5 Reasons Cancer Researchers Adopt 3D Cell Culture White Paper

5 Reasons Cancer Researchers
Adopt 3D Cell Culture:

A Review of Recent Literature
Summary
Numerous cancer model systems are available to
investigate disease mechanisms and to screen therapies. While
all of the models have contributed critical information about
Contents
6
Growing cells in 3D
alters cell
proliferation and
morphology.
Growing cells in 3D
reveals a more
realistic drug
response.
Growing cells in 3D
captures
phenotypic
heterogeneity.
cancer biology, current tools have significant problems. Roughly

90% of promising preclinical drugs, in all therapeutic classes, fail
to result in efficacious human treatments, thereby wasting vast
amounts of time and money and, ultimately, delaying the
discovery of successful interventions (van der Worp et al., 2010).
In the most simplistic view, two-dimensional (2D) tissue culture
models lack realistic complexity, while animal models are
expensive, time consuming, and too frequently fail to reflect
human tumor biology (Aggarwal et al., 2009; Hait, 2010; van der
11 Growing cells in 3D
changes gene
expression and cell
behavior.
Worp et al., 2010). This white paper presents five alterations in

cellular physiology that suggest why three-dimensional (3D)
12 Growing cells in 3D
mimics the tumor
microenvironment.
cultures of cancer cells are a scientifically-rigorous method to

generate new drug candidates before moving to expensive and
time-consuming animal models. Adding 3D culture to your
laboratorys repertoire can speed discovery and save money
when developing cancer models for preclinical screening and
testing, as well as for new therapy research and development.
Cover image A model image

of p53 biding to DNA. This
protein is mutated or deleted in
more than 50% of human
tumors.
iStockphoto.com/Martin
McCarthy.
White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

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Page 2
Figure 1
Epithelial tumor
and surrounding
environment, a
complex biology
to model. Image
from Kimlin et al.,
2013
Introduction
Preclinical cancer drug research has the worst success rate of any therapeutic area with a
paltry 5% of candidate compounds passing phase III clinical trials for safety and efficacy (Hutchinson
and Kirk, 2011). Researchers have devised a vast array of model systems to study the complex
components of tumors (Figure 1) and their treatment, each with unique advantages and
disadvantages. All models have two key requirements. The first is the ability to monitor cell number
and viability since a key characteristic of cancer is uncontrolled cell proliferation sustained by multiple
mechanisms. The second is the capacity to study migration and invasion of cancerous cells into
surrounding tissues, as metastasis not only damages surrounding tissue, but also complicates
treatment. Complex and desirable, yet challenging-to-model features include angiogenesis
stimulation and immune system evasion, both of which contribute to long-term tumor survival. The
best preclinical model would be relatively inexpensive, amenable to high-throughput screening, and
most importantly, reflect human-tumor biology as closely as possible.
Page 3
The most simplistic cancer models are cell lines derived from human and animal tumors grown
as flat monolayers submerged in media. In this configuration, cells are adhering to an artificial plastic
or glass substrate and in contact with other cells only at their periphery. Oxygen, nutrient, or waste
gradients are not present; the environment is non-physiologically uniform. Coating dishes with
extracellular matrix (ECM) can restore a more natural basal adhesion; however, unless the cells are
allowed to pile on top of one another they are still being forced into a monolayer morphology, which is
not natural for all cell types. Establishing co-cultures in a flat dish can increase natural intercellular
contact and communication, but the 2D surface still inhibits the ability for cells to form a multidimensional structure. Cells grown in flat layers on plastic surfaces simply do not reflect the
multicellular microenvironment found in the body. There is no doubt that immortalized tumor lines
grown in 2D culture have contributed tremendous amounts of knowledge about the mechanism of
cancer, but with a 95% drug failure rate, (Hutchinson and Kirk, 2011) they have proven a poor drug
development model.
Figure 2
Rodent cancer models. Image adapted from Francia and Kerbel, 2010
Animal models have been used as living incubators in which human tumors have been grown,
thereby interacting with a whole organism, albeit frequently an immunodeficient one. Cancer is
established in rodent models by either surgically implanting tumor cells or creating geneticallyengineered animals that spontaneously develop human-like tumors in response to experimental
modification of gene expression (Figure 2).
Page 4
At first glance, this seems an inherently desirable system in which to mimic human disease. Despite
extensive use for screening, these expensive animal models have failed to develop into therapies that
translate to improved outcomes for human disease (Aggarwal et al., 2009; Hait, 2010; van der Worp,
et al., 2010). In addition, there are many forms of deadly cancer that currently lack a qualified animal
model including brain, kidney, and skin (Steele and Lubet, 2010). The reasons for animal model
failures are not completely understood. Determining why will ultimately lead to increased
understanding of the disease process, but at present theses models are clearly not generating
therapies with a high rate of return on investment.
Scientists have been developing 3D tissue culture models to bridge the gap between in vitro
experiments used for discovery and screening and in vivo experiments used for efficacy and safety
assessment before proceeding to clinical trials. It is logical to use 3D models with customized
microenvironments to dissect cancer biology and establish therapeutic screens, and the evidence
that they are a superior system to 2D and early-stage animal testing is rapidly emerging.
The
purpose of this white paper is to briefly review recent 3D cell culture publications that exemplify the
scientific merit of the 3D technique for understanding cancer biology.

Page 5
1. Growing Cells in 3D alters proliferation

and cell morphology.
When cancer cells are grown in a flat monolayer,
they proliferate at a relatively uniform rate across the
surface. However, growing the same cells in 3D induces
zones of differential proliferation (Figure 3) with cell
division occurring more rapidly on
the outside of the spheroid (Lin and
Chang,
2008).
Generally
this
results in a mild reduction in the

rate of proliferation for some, but
not all, cancer cell lines examined
(Chitcholtan, et al., 2013; Longati et
al., 2013; Myungjin Lee et al.,
2013; Zschenker et al., 2012). The
suggested
mechanisms
for
Figure 3
Growth of cells in spheroids results in differential zones of
proliferation due to oxygen, nutrient, and waste gradients.
Figure from Lin and Chang, 2008.
changes in proliferation rate include

oxygen/nutrient/growth factor gradients across the
spheroid (Lin and Chang 2008), ECM-dependent
changes in intracellular signaling, (Kim et al., 2011,
Tibbitt and Anseth, 2012), and stromal cell influence
(McMillin et al., 2013).

Page 6
Growth of cells on a 2D surface results in correspondingly flat cells through simple geometry;
there is only one surface on which to adhere. Forcing one side to adhere to a substrate with no
opportunity for cellular contact on the opposite side results in default apical-basal polarity and
changes in cell shape that ultimately modify cellular function (Baker and Chen, 2012). Merely
growing tumor cell lines in 3D, even ovarian epithelial cells with default apical-basal polarity (Figure
4), induces histological morphology reminiscent of the tumor type from which they were derived
(Myungjin Lee et al., 2013). When the same ovarian epithelia lines were grown in 2D there was no
such histological differentiation. Culture of selected prostate and breast cancer cell lines
encapsulated in Matrigel revealed either spheroidal or stellate cellular morphology indicative of
differences in invasive behavior (Hama et al., 2010). However, similar experiments with endometrial
and colon cancer lines failed to generate morphology that was predictive of invasive behavior
(Chitcholtan, et al., 2013; Luca et al., 2013). The variable responses to 3D culture in Matrigel
highlight innate variations in malignancies from diverse organs as well as how the microenvironment
influences cells to produce clinically-relevant observations. Thus, 3D culture can be used to study
tumor morphology and understand differences between lines from tumors of similar and dissimilar
organs and tissues.
Figure 4
OAW42 epithelial ovarian cancer cells grown in 2D and 3D, the later of which resembles the
well-differentiated (Grade 1) serous ovarian tumor shown on the far right. The 3D culture even
contains a psammoma body (arrow), a calcified circular structure found in some tumors. Image
adapted from (Myungjin Lee et al., 2013).
Page 7
2. Growing cells in 3D reveals a more

realistic drug response.
Growing cells as 3D spheroids can increase resistance to chemotherapy when compared to
the same cells grown in monolayers. The most straightforward explanation for enhanced resistance
is that the cells on the inside of the spheroid are protected from drug penetration by the cells on the
outside of the spheroid (Perche and Torchilin, 2012). Another mechanism has been suggested
related to the differential zones of proliferation described above (Chitcholtan et al., 2013). Some
Figure 5
chemotherapeutics, like cisplatin, work by

Leukemic 3D
cultures were
more resistant
to doxorubicin
than 2D cultures
despite equal
penetrance of
drug into both
models. Image
from (Aljitawi et
al., 2013).
inducing DNA damage in proliferating

cells severe enough to induce apoptosis.
The quiescent population sequestered on
the inside of the spheroid will remain
protected from drugs like cisplatin, then
be free to re-enter the cell cycle once the
outer cells are dead. If therapy is halted
too early, these protected cells may be able to recapitulate a tumor that was shrunk but not
completed killed. The mechanisms of drug resistance are likely to be more complicated than just
failure to fully penetrate a tumor in vivo and reflected in vitro by spheroid biology. When leukemic cell
lines were co-cultured with bone marrow mesenchymal stem cells in either a 2D or 3D system
(Figure 5), the 3D culture provided chemoprotection from doxorubicin compared to the 2D culture,
despite experiments illustrating that both models allowed complete penetration of the drug (Aljitawi et
al., 2013).

Page 8
In addition, pancreatic cancer cell lines as well as freshly isolated pancreatic cells from a pancreatic
cancer mouse model demonstrated increased expression of several drug resistance genes and
microRNAs leading to increased drug resistance in 3D culture as compared to 2D culture (Longati et
al., 2013). These results demonstrate that 3D culture recapitulate several mechanisms of drug
resistance found in tumors in vivo, offering the opportunity to dissect the mechanisms and test multidrug therapy regimens in vitro before proceeding to animal models and ultimately clinical trials.
3. Growing cells in 3D captures

phenotypic heterogeneity.
Heterogeneity occurs across a population of cells within the same tumor as marked by
changes in proliferation rate, gene expression, and differentiation resulting in morphological and
functional changes (Marjanovic et al., 2013). Wide varieties of phenotypic behavior make targeting
drugs to kill the entire tumor challenging since the physiologies can be so divergent. Two theories
exist to explain these differences. The clonal selection theory postulates that phenotypic and
genotypic heterogeneity is brought about by genetic instability leading to mutations, and perhaps
epigenetic changes followed by selection due to competition between cells of an individual tumor
(Kreso et al., 2013; Marusyk and Polyak, 2013). Selection pressure could be due to the stress of
nutrient deprivation, from tumor growth, or drug treatment. Since tumor spheroids have oxygen and
nutrient gradients, 3D models could be established to test these theories with greater ease than
serially-passaged mouse xenograft tumors. In fact, a 3D model of ovarian epithelial cancer initiation
and progession has been created to study these exact types of genetic changes (Lawrenson et al.,
2011).

Page 9
Figure 6
Rare purported cancer stem cells survive (CSCs) traditional chemotherapeutic
treatments and can recapitulate the entire tumor including a new subset of CSCs.
Image adapted from Vermeulen et al., 2012.
A second controversial theory hypothesizes that cancer stem cells (CSCs) exist that either
seek out a niche created within the tumor microenvironment or are created by signals from a niche
itself (Borovski et al., 2011). A miniscule number of cells of an in vitro spheroid or an in vivo tumor
exhibit characteristics of stem cell-like characteristics including a slowed proliferation rate, selfrenewal and an undifferentiated phenotype that can undergo multilineage differentiation (Schiavoni et
al., 2013). CSCs, which can reconstitute tumors following drug treatment (Figure 6), have been
described in both 3D spheroid models and in patients undergoing chemotherapy (Chitcholtan et al.,
2012). Increased expression of stemness-related genes (Busse et al., 2013) was observed when
comparing solid tumor cell lines grown as 3D spheroids to monolayers. While clearly not definitive
proof of the presence of CSCs, these types of results illustrate the tendency for the in vitro 3D
microenvironment to create a stem cell-like population similar to the in vivo population believed to
be responsible for tumor drug resistance. For arduous to treat and therefore deadly cancers, like
glioblastoma, characterizing and reproducing the microenvironment responsible for initiation and
survival of CSCs in vitro may be the quickest pathway to potential treatment (Filatova et al., 2013).

Page 10
4. Growing cells in 3D changes gene

expression and cell behavior.
Cells grown in 3D cultures generate divergent gene expression patterns when compared to
the exact same cells grown as a monolayer (Myungjin Lee et al., 2013; Luca et al., 2013). Differential
extracellular interactions with ECM (Figure 7) and stromal cells in 3D or 3D co-culture models change
intracellular signal transduction, culminating in activation of a unique set of transcription factors in 2D
versus 3D models (Bellis et al., 2012). Since transcription factors are ultimately responsible for gene
expression, changes in cell contact directly results in changes in gene expression. As discussed
above, these gene expression changes drive changes in morphology, proliferation rates, and drug
resistance, all of which promote a more representative cancer tissue. In turn, these changes in tumor
gene expression can alter intercellular feedback to other cells within the culture by modifying the
secretion of ECM or signaling factors (Longati et al.,2013).
Figure 7
One hypothesis for how ECM controls
intracellular signaling is through the binding
of different subtypes of transmembrane
integrin proteins. Integrins then interact with
various intracellular adaptor proteins to form
a focal adhesion complex that regulates
signaling pathways downstream of growth
factor receptors. Image adapted from Kim et
al, 2011.

Page 11
The culmination of these genetic changes has impacts on cell behaviors such as cell
migration and differentiation that are inexorably linked to the severity of tumor progression.
Typically cell migration has been interrogated in Boyden chamber systems or monolayer scratch
assays, but concerted effort is being put forth to reimagine these assays in the more sophisticated
3D environments because the results are more likely to be clinically relevant (Burgstaller et al.,
2012). The differences in cell behavior between normal somatic cells and tumor cells grown in 3D
can be so pronounced that there is potential to distinguish normal from transformed cells just by
growing them in 3D (Fassert et al., 2013). When normal human bronchial epithelial cells are
grown in 2D cultures they proliferate until they form a confluent monolayer, but in 3D Matrigel
cultures, they differentiate into a characteristic lumen-containing glandular structure, termed an
acinus (Wu at al., 2011). When several different epithelial lung cancer lines were grown in 3D
Matrigel cultures they formed more spheroids per cell number seeded that failed to differentiate
and form a lumen, instead simply increasing in size. The potential of 3D cultures in understanding
cancer and perhaps even someday for rapid diagnostic screens are just beginning to be realized.
5. Growing cells in 3D mimics the tumor

microenvironment.
As illustrated by all the examples above, cells being grown in 3D cultures much more closely
resemble the cells growing within living tumors. One of the most exciting facets of creating in vitro
3D cancer models is the ability to experimentally manipulate each component of the tumor
microenvironment to try and understand the drivers of cancer as a disease state. Take for example
the groundbreaking work of Mina Bissell, whose lab was among the first to recognize that when
normal mammary epithelial cells were grown in monolayers they divided exponentially through
several passages.
Page 12
However, when mammary epithelial cells were grown in 3D Matrigel culture, they responded to
microenvironmental signals by reducing proliferation and differentiating into nearly normal-sized
mammary acinar structures (Figure 8) (Petersen et al., 1992; Tibbitt and Anseth, 2012). Cells derived
from breast carcinomas were unable to respond to signals within the Matrigel microenvironment,
continuing to divide and failing to form a lumen. By extension, this implies that cancer is a disease of
not only the tumor cell but also the surrounding microenvironment. This has important implications
for cell lines that have been established and propagated as monolayers. There is no doubt that longterm passage of cells as monolayers could result in loss of the ability to respond to external signals.
This could partially explain why cancer cell lines, when returned to a 3D environment, have an
incomplete restoration of the original cancer phenotype. In fact, establishing robust spheroid cultures
from primary patient samples of colon cancer required the maintenance of some cellular contact as
clusters to prevent death (Kondo et al., 2011). Establishing monolayers from tumors may select for
rare cells that are able to survive in a highly unnatural environment, perhaps not the best material for
modeling tumors.
Figure 8
Diagram of a mammary acinus on left and a morphologically similar 3D culture derived MCF10A acinus on right. The lumens of the in vitro derived acini even contain secreted material
on the inside (arrow). Image adapted from Debnath et al., 2003.

Page 13
No discussion of tumor microenvironment would be complete without mentioning the

burgeoning role for cancer-associated fibroblasts (CAFs) in disease progression. The origin of these
cells is currently not well understood, but they appear to play a crucial role in the establishment and
maintenance of the tumor microenvironment (Allen and Jones 2011; Cirri and Chiarugi, 2011). There
is some evidence that signals emanating from the cancer cells within the tumor activate surrounding
stromal cells to become CAFs (Figure 9). Normal fibroblasts secrete ECM that comprises the
scaffold on which the stromal compartment is arranged. CAFs secrete ECM with an altered protein
profile that when compared to normal fibroblasts can have a profound effect on the behavior of tumor
cells. In addition, CAFs secrete a variety of growth factors that stimulate proliferation of tumor cells.
Based on the growing evidence that CAFs influence tumor proliferation and metastasis, they are
emerging as a critical target for combinatorial cancer drug therapies. Including CAFs in a 3D cancer
model can increase the understanding of their role in tumor progression and uncover new potential
therapies that would remain undiscovered in monolayer models.
Figure 9
Cancer cells initiate the progression from fibroblast to CAF via a process called
MMT (mesenchymal-mesenchymal transition). CAFs then provide a variety of growth factor
signals and secrete ECM that promotes the progression, survival, and migration of cancer
cells. Image adapted from Cirri and Chiarugi, 2011.

Page 14
Conclusions
Recapitulating a tumor in vitro requires that all components of the tumor are present, to
reproduce typical cell morphology and function, the ECM, proliferating tumor cells, CSC, and stromal
cells. The tremendous flexibility of 3D cultures created in Perfecta3D Hanging Drop Plates allows
for the experimental manipulation of all these variables (Figure 10). Each one of these components
influences the biology and behavior of the other components, culminating in the functioning tumor
model. When cells are removed from a tumor and grown in a monolayer on tissue culture plastic, the
loss of these interactions changes their behavior and results in a substandard model for
understanding biology or establishing appropriate therapies. This is reflected in the tremendous
number of drugs that kill cancerous monolayers, but fail to demonstrate clinical relevance.
Carefully controlling all of the variables discussed above increases the probability that a
cancer model is more likely to accurately represent the tumor microenvironment. 3D models can be
even more realistic and controllable than human cancer animal xenografts where tumor cells are
often transplanted to sites that, while convenient for tumor observation, do not reflect the
microenvironment of the original tumor.
Figure 10
A schematic of the Perfecta3D Hanging Drop Plate. Cultures can be established with a single
cell type or as co-cultures, a wide range of starting cell numbers, and with or without addition of
exogenous ECM.

Page 15
Even when the transplantation site is orthotopic, species differences between rodent and human
physiology may result in a failure to establish the intricate tumor microenvironment. Despite these
limitations, there are certain aspects of efficacy and toxicity that will always require evaluation in
animal models prior to human clinical trails. However, preclinical studies that utilize the advantages of
3D culture early on can greatly improve the understanding of cancer biology, eliminate poor drug
candidates, and, most promisingly, reveal new more physiologically-relevant targets that might have
been missed in 2D screens. Establishing a 3D model system can save time and money by generating
more significantly realistic results earlier.
For more information on

establishing 3D cultures
please visit our 3D Cell
Culture Knowledge Center at
www.3DBiomatrix.com.

Page 16
References
Aggarwal, B. B., D. Danda, et al. (2009). "Models for prevention and treatment of cancer: problems
vs promises." Biochemical pharmacology 78(9): 1083-1094.
Aljitawi, O. S., D. Li, et al. (2013). "A novel three-dimensional stromal-based model for in vitro
chemotherapy sensitivity testing of leukemia cells." Leukemia & lymphoma.
Allen, M. and J. Louise Jones (2011). "Jekyll and Hyde: the role of the microenvironment on the
progression of cancer." The Journal of pathology 223(2): 162-176.
Baker, B. M. and C. S. Chen (2012). "Deconstructing the third dimension: how 3D culture
microenvironments alter cellular cues." Journal of cell science 125(Pt 13): 3015-3024.
Bellis, A. D., B. P. Bernabe, et al. (2013). "Dynamic transcription factor activity profiling in 2D and 3D
cell cultures." Biotechnology and bioengineering 110(2): 563-572.
Borovski, T., E. M. F. De Sousa, et al. (2011). "Cancer stem cell niche: the place to be." Cancer
research 71(3): 634-639.
Burgstaller, G., B. Oehrle, et al. (2013). "Multiplex Profiling of Cellular Invasion in 3D Cell Culture
Models." PloS one 8(5): e63121.
Busse, A., A. Letsch, et al. (2013). "Characterization of small spheres derived from various solid
tumor cell lines: are they suitable targets for T cells?" Clinical & experimental metastasis.
Chitcholtan, K., E. Asselin, et al. (2013). "Differences in growth properties of endometrial cancer in
three dimensional (3D) culture and 2D cell monolayer." Experimental cell research 319(1): 75-87.
Chitcholtan, K., P. H. Sykes, et al. (2012). "The resistance of intracellular mediators to doxorubicin
and cisplatin are distinct in 3D and 2D endometrial cancer." Journal of translational medicine 10: 38.
Cirri, P. and P. Chiarugi (2011). "Cancer associated fibroblasts: the dark side of the coin." American
journal of cancer research 1(4): 482-497.
Debnath, J., S. K. Muthuswamy, et al. (2003). "Morphogenesis and oncogenesis of MCF-10A
mammary epithelial acini grown in three-dimensional basement membrane cultures." Methods 30(3):
256-268.
Fessart, D., H. Begueret, et al. (2013). "3D culture model to distinguish normal from malignant
human bronchial epithelial cells." The European respiratory journal : official journal of the European
Society for Clinical Respiratory Physiology.

Page 17
Filatova, A., T. Acker, et al. (2013). "The cancer stem cell niche(s): the crosstalk between glioma
stem cells and their microenvironment." Biochimica et biophysica acta 1830(2): 2496-2508.
Francia, G. and R. S. Kerbel (2010). "Raising the bar for cancer therapy models." Nature
biotechnology 28(6): 561-562.
Hait, W. N. (2010). "Anticancer drug development: the grand challenges." Nature reviews. Drug
discovery 9(4): 253-254.
Harma, V., J. Virtanen, et al. (2010). "A comprehensive panel of three-dimensional models for
studies of prostate cancer growth, invasion and drug responses." PloS one 5(5): e10431.
Hutchinson, L. and R. Kirk (2011). "High drug attrition rates--where are we going wrong?" Nature
reviews. Clinical oncology 8(4): 189-190.
Kim, S. H., J. Turnbull, et al. (2011). "Extracellular matrix and cell signalling: the dynamic
cooperation of integrin, proteoglycan and growth factor receptor." The Journal of endocrinology
209(2): 139-151.
Kimlin, L. C., G. Casagrande, et al. (2013). "In vitro three-dimensional (3D) models in cancer
research: an update." Molecular carcinogenesis 52(3): 167-182.
Kondo, J., H. Endo, et al. (2011). "Retaining cell-cell contact enables preparation and culture of
spheroids composed of pure primary cancer cells from colorectal cancer." Proceedings of the
National Academy of Sciences of the United States of America 108(15): 6235-6240.
Kreso, A., C. A. O'Brien, et al. (2013). "Variable clonal repopulation dynamics influence
chemotherapy response in colorectal cancer." Science 339(6119): 543-548.
Lawrenson, K., D. Sproul, et al. (2011). "Modelling genetic and clinical heterogeneity in epithelial
ovarian cancers." Carcinogenesis 32(10): 1540-1549.
Lin, R. Z. and H. Y. Chang (2008). "Recent advances in three-dimensional multicellular spheroid
culture for biomedical research." Biotechnology journal 3(9-10): 1172-1184.
Longati, P., X. Jia, et al. (2013). "3D pancreatic carcinoma spheroids induce a matrix-rich,
chemoresistant phenotype offering a better model for drug testing." BMC cancer 13: 95.
Luca, A. C., S. Mersch, et al. (2013). "Impact of the 3D microenvironment on phenotype, gene
expression, and EGFR inhibition of colorectal cancer cell lines." PloS one 8(3): e59689.
Marjanovic, N. D., R. A. Weinberg, et al. (2013). "Cell plasticity and heterogeneity in cancer." Clinical
chemistry 59(1): 168-179.
Marusyk, A. and K. Polyak (2013). "Cancer. Cancer cell phenotypes, in fifty shades of grey." Science
339(6119): 528-529.

Page 18
McMillin, D. W., J. M. Negri, et al. (2013). "The role of tumour-stromal interactions in modifying drug
response: challenges and opportunities." Nature reviews. Drug discovery 12(3): 217-228.
Myungjin Lee, J., P. Mhawech-Fauceglia, et al. (2013). "A three-dimensional microenvironment alters
protein expression and chemosensitivity of epithelial ovarian cancer cells in vitro." Laboratory
investigation; a journal of technical methods and pathology 93(5): 528-542.
Perche, F. and V. P. Torchilin (2012). "Cancer cell spheroids as a model to evaluate chemotherapy
protocols." Cancer biology & therapy 13(12): 1205-1213.
Petersen, O. W., L. Ronnov-Jessen, et al. (1992). "Interaction with basement membrane serves to
rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial
cells." Proceedings of the National Academy of Sciences of the United States of America 89(19):
9064-9068.
Schiavoni, G., L. Gabriele, et al. (2013). "The tumor microenvironment: a pitch for multiple players."
Frontiers in oncology 3: 90.
Steele, V. E. and R. A. Lubet (2010). "The use of animal models for cancer chemoprevention drug
development." Seminars in oncology 37(4): 327-338.
Tibbitt, M. W. and K. S. Anseth (2012). "Dynamic microenvironments: the fourth dimension." Science
translational medicine 4(160): 160ps124.
van der Worp, H. B., D. W. Howells, et al. (2010). "Can animal models of disease reliably inform
human studies?" PLoS medicine 7(3): e1000245.
Vermeulen, L., F. de Sousa e Melo, et al. (2012). "The developing cancer stem-cell model: clinical
challenges and opportunities." The lancet oncology 13(2): e83-89.
Wu, X., J. R. Peters-Hall, et al. (2011). "Human bronchial epithelial cells differentiate to 3D glandular
acini on basement membrane matrix." American journal of respiratory cell and molecular biology
44(6): 914-921.
Zschenker, O., T. Streichert, et al. (2012). "Genome-wide gene expression analysis in cancer cells
reveals 3D growth to affect ECM and processes associated with cell adhesion but not DNA repair."
PloS one 7(4): e34279.

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5 Reasons Cancer Researchers

Adopt 3D Cell Culture:

cancer biology, current tools have significant problems. Roughly

Worp et al., 2010). This white paper presents five alterations in

cultures of cancer cells are a scientifically-rigorous method to

Cover image A model image

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

1. Growing Cells in 3D alters proliferation

results in a mild reduction in the

changes in proliferation rate include

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

2. Growing cells in 3D reveals a more

chemotherapeutics, like cisplatin, work by

inducing DNA damage in proliferating

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

3. Growing cells in 3D captures

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

4. Growing cells in 3D changes gene

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

5. Growing cells in 3D mimics the tumor

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

No discussion of tumor microenvironment would be complete without mentioning the

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

For more information on

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

White paper - 5 Reasons Cancer Researchers Adopt 3D Cell Culture

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