Modelling glandular epithelial cancers in three-dimensional cultures

Nature Reviews Cancer

Volumn 5, Issue 9, 2005, Pages 675-688

  Debnath, Jayanta ^a,b   Brugge, Joan S ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; COLONY STIMULATING FACTOR 1; EVEROLIMUS; RAPAMYCIN; TRANSFORMING GROWTH FACTOR BETA;

ADENOCARCINOMA; APOPTOSIS; BREAST CANCER; CANCER CELL CULTURE; CANCER GENETICS; CANCER MODEL; CARCINOGENESIS; CELL GROWTH; CELL MIGRATION; CELL POLARITY; CELL PROLIFERATION; CELL STRUCTURE; GENOTYPE; HUMAN; IN VIVO CULTURE; MORPHOGENESIS; NONHUMAN; ONCOGENE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TUMOR GROWTH; ANIMAL; BIOLOGICAL MODEL; CELL TRANSFORMATION; CULTURE TECHNIQUE; CYTOLOGY; EPITHELIUM CELL; GENETICS; IN VITRO STUDY; METHODOLOGY; NEOPLASM; PATHOLOGY;

ANIMALS; CELL CULTURE TECHNIQUES; CELL TRANSFORMATION, NEOPLASTIC; EPITHELIAL CELLS; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS;

EID: 25444443688     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc1695     Document Type: Review

References (145)

1. Bissell, M. J., Radisky, D. C., Rizki, A., Weaver, V. M. & Petersen, O. W. The organizing principle: microenvironmental influences in the normal and malignant breast. Differentiation 70, 537-546 (2002).
2. O'Brien, L. E., Zegers, M. M. & Mostov, K. E. Building epithelial architecture: insights from three-dimensional culture models. Nature Rev. Mol. Cell. Biol. 3, 531-537 (2002).
3. Rodriguez-Boulan, E. & Nelson, W. J. Morphogenesis of the polarized epithelial cell phenotype. Science 245, 718-725 (1989).
4. Toikkanen, S., Pylkkanen, L. & Joensuu, H. Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma. Br. J. Cancer 76, 1234-1240 (1997).
5. Simpson, J. F. & Page, D. L. Pathology of preinvasive and excellent prognosis breast cancer. Curr. Opin. Oncol. 13, 426-430 (2001).
6. Berx, G. et al. E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene 13, 1919-1925 (1996).
7. van de Vijver, M. J. et al. NEU-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N. Engl. J. Med. 319, 1239-1245 (1988).
8. Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747-752 (2000).
9. Ramaswamy, S. et al. Multiclass cancer diagnosis using tumor gene expression signatures. Proc. Natl Acad. Sci. USA 98, 15149-15154 (2001).
10. Ma, X. J. et al. Gene expression profiles of human breast cancer progression. Proc. Natl Acad. Sci. USA 100, 5974-5979 (2003).
11. Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57-70 (2000).
12. Schmeichel, K. L. & Bissell, M. J. Modeling tissue-specific signaling and organ function in three dimensions. J. Cell Sci. 116, 2377-2388 (2003).
13. Streuli, C. H. & Bissell, M. J. Expression of extracellular matrix components is regulated by substratum. J. Cell. Biol. 110, 1405-1415 (1990).
14. Petersen, O. W., Ronnov-Jessen, L., Howlett, A. R. & Bissell, M. J. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc. Natl Acad. Sci. USA 89, 9064-9068 (1992). Illustrates the stark phenotypic contrasts between normal cells and tumour cells when grown in 3D basement membrane cultures; by comparison, only subtle differences in morphology are evident when the same cells are grown as monolayers.
15. Debnath, J., Muthuswamy, S. K. & Brugge, J. S. Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30, 256-268 (2003).
16. Kenny, P. A. & Bissell, M. J. Tumor reversion: correction of malignant behavior by microenvironmental cues. Int. J. Cancer 107, 688-695 (2003).
17. Briand, P., Petersen, O. W. & Van Deurs, B. A new diploid nontumorigenic human breast epithelial cell line isolated and propagated in chemically defined medium. In Vitro Cell Dev. Biol. 23, 181-188 (1987).
18. Nielsen, K. V., Madsen, M. W. & Briand, P. In vitro karyotype evolution and cytogenetic instability in the nontumorigenic human breast epithelial cell line HMT-3522. Cancer Genet. Cytogenet. 78, 189-199 (1994).
19. Weaver, V. M. et al. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J. Cell. Biol. 137, 231-245 (1997). Describes a series of mammary cell lines that display progressive loss of their ability to form growth arrested structures in 3D EHS cultures, as well as increased genomic instability, and upregulation of the ECM receptor β1-integrin. The report demonstrates that reductions in β1-integrin signalling can suppress tumorigenicity.
20. Wang, F. et al. Reciprocal interactions between β1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. Proc. Natl Acad. Sci. USA 95, 14821-14826 (1998).
21. Wang, F. et al. Phenotypic reversion or death of cancer cells by altering signaling pathways in three-dimensional contexts. J. Natl Cancer Inst. 94, 1494-2503 (2002).
22. Muschler, J. et al. A role for dystroglycan in epithelial polarization: loss of function in breast tumor cells. Cancer Res. 62, 7102-7109 (2002).
23. Henry, M. D., Cohen, M. B. & Campbell, K. P. Reduced expression of dystroglycan in breast and prostate cancer. Hum. Pathol. 32, 791-795 (2001).
24. Weir, M. L. & Muschler, J. Dystroglycan: emerging roles in mammary gland function. J. Mammary Gland Biol. Neoplasia 8, 409-419 (2003).
25. 2β1 integrin abrogates the malignant phenotype of breast carcinoma cells. Proc. Natl Acad. Sci. USA 92, 7411-7415 (1995). Provided one of the first demonstrations that perturbation of integrin receptors can cause reversion of aberrant morphogenesis in 3D basement-membrane cultures.
26. Kirshner, J., Chen, C. J., Liu, P., Huang, J. & Shively, J. E. CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture. Proc. Natl Acad. Sci. USA 100, 521-526 (2003).
27. Hirschi, K. K., Xu, C. E., Tsukamoto, T. & Sager, R. Gap junction genes CX26 and CX43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential. Cell Growth Differ. 7, 861-870 (1996).
28. Hall, H. G., Farson, D. A. & Bissell, M. J. Lumen formation by epithelial cell lines in response to collagen overlay: a morphogenetic model in culture. Proc. Natl Acad. Sci. USA 79, 4672-4676 (1982).
29. Ojakian, G. K., Nelson, W. J. & Beck, K. A. Mechanisms for de novo biogenesis of an apical membrane compartment in groups of simple epithelial cells surrounded by extracellular matrix. J. Cell Sci. 110, 2781-2794. (1997).
30. Hoffman, M. P., Kibbey, M. C., Letterio, J. J. & Kleinman, H. K. Role of laminin-1 and TGF-β 3 in acinar differentiation of a human submandibular gland cell line (HSG). J. Cell Sci. 109, 2013-2021. (1996).
31. Blatchford, D. R. et al. Influence of microenvironment on mammary epithelial cell survival in primary culture. J. Cell. Physiol. 181, 304-311 (1999).
32. Huang, J., Hardy, J. D., Sun, Y. & Shively, J. E. Essential role of biliary glycoprotein (CD66a) in morphogenesis of the human mammary epithelial cell line MCF10F. J. Cell Sci. 112, 4193-4205 (1999).
33. Lin, H. H., Yang, T. P., Jiang, S. T., Yang, H. Y. & Tang, M. J. BCL2 overexpression prevents apoptosis-induced Madin-Darby canine kidney simple epithelial cyst formation. Kidney Int. 55, 168-178 (1999).
34. Debnath, J. et al. The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell 111, 29-40 (2002). Demonstrates that apoptosis has a crucial role in the formation and maintenance of the lumen in MCF-10A epithelial acini and shows that a hollow 3D architecture is resistant to isolated proliferative oncogenes that lack anti-apoptotic activity. In addition, it shows that alternate processes can mediate lumen formation when apoptosis is blocked.
35. Boudreau, N., Sympson, C. J., Werb, Z. & Bissell, M. J. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science 267, 891-893 (1995).
36. Frisch, S. M., Vuori, K., Ruoslahti, E. & Chan-Hui, P. Y. Control of adhesion-dependent cell survival by focal adhesion kinase. J. Cell. Biol. 134, 793-799 (1996).
37. Reginato, M. J. et al. BIM regulation of lumen formation in cultured mammary epithelial acini is targeted by oncogenes. Mol. Cell. Biol. 25, 4591-4601 (2005).
38. Reginato, M. J. et al. Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nature Cell Biol. 5, 733-740 (2003).
39. Humphreys, R. C. et al. Apoptosis in the terminal endbud of the murine mammary gland: a mechanism of ductal morphogenesis. Development 122, 4013-4022 (1996).
40. Huang, J. et al. Expression of biliary glycoprotein (CD66a) in normal and malignant breast epithelial cells. Anticancer Res. 18, 3203-3212 (1998).
41. Neumaier, M., Paululat, S., Chan, A., Matthaes, P. & Wagener, C. Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas. Proc. Natl Acad. Sci. USA 90, 10744-10748 (1993).
42. Kirshner, J., Hardy, J., Wilczynski, S. & Shively, J. E. Cell-cell adhesion molecule CEACAM1 is expressed in normal breast and milk and associates with β1 integrin in a 3D model of morphogenesis. J. Mol. Histol. 35, 287-299 (2004).
43. Hirai, Y. et al. Epimorphin functions as a key morphoregulator for mammary epithelial cells. J. Cell. Biol. 140, 159-169 (1998).
44. Hirai, Y. et al. Epimorphin mediates mammary luminal morphogenesis through control of C/EBPβ. J. Cell. Biol. 153, 785-794 (2001).
45. Muthuswamy, S. K., Li, D., Lelievre, S., Bissell, M. J. & Brugge, J. S. ERBB2, but not ERBB1, reinitiates proliferation and induces luminal repopulation in epithelial acini. Nature Cell Biol. 3, 785-792 (2001). Shows that the inducible dimerization of two closely related receptor tyrosine kinases of the EGFR family - ERBB1 and ERBB2 - elicits distinct and unexpected effects on 3D epithelial architecture.
46. Wrobel, C. N. et al. Autocrine CSF-1R activation promotes SRC-dependent disruption of mammary epithelial architecture. J. Cell. Biol. 165, 263-273 (2004).
47. Liu, X. W. et al. Tissue inhibitor of metalloproteinase-1 protects human breast epithelial cells from extrinsic cell death: a potential oncogenic activity of tissue inhibitor of metalloproteinase-1. Cancer Res. 65, 898-906 (2005).
48. Humbert, P., Russell, S. & Richardson, H. DLG, SCRIBBLE and LGL in cell polarity, cell proliferation and cancer. Bioessays 25, 542-553 (2003).
49. Knust, E. & Bossinger, O. Composition and formation of intercellular junctions in epithelial cells. Science 298, 1955-1959 (2002).
50. Schoenenberger, C. A., Zuk, A., Kendall, D. & Matlin, K. S. Multilayering and loss of apical polarity in MDCK cells transformed with viral K-RAS. J. Cell. Biol. 112, 873-889 (1991).
51. Warren, S. L., Handel, L. M. & Nelson, W. J. Elevated expression of PP60c-SRC alters a selective morphogenetic property of epithelial cells in vitro without a mitogenic effect. Mol. Cell. Biol. 8, 632-646 (1988).
52. Liu, H., Radisky, D. C., Wang, F. & Bissell, M. J. Polarity and proliferation are controlled by distinct signaling pathways downstream of PI3-kinase in breast epithelial tumor cells. J. Cell. Biol. 164, 603-612 (2004).
53. Forcet, C. et al. Functional analysis of Peutz-Jeghers mutations reveals that the LKB1 carboxy-terminal region exerts a crucial role in regulating both the AMPK pathway and cell polarity. Hum. Mol. Genet. 30 March 2005 (doi: 10.1093/hmg/ddi139).
54. Baas, A. F. et al. Complete polarization of single intestinal epithelial cells upon activation of LKB1 by STRAD. Cell 116, 457-466 (2004).
55. Bilder, D., Li, M. & Perrimon, N. Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289, 113-116 (2000).
56. Nakagawa, S. & Huibregtse, J. M. Human SCRIBBLE (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol. Cell. Biol. 20, 8244-8253 (2000).
57. Kiyono, T. et al. Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. Proc. Natl Acad. Sci. USA 94, 11612-11616 (1997).
58. Lee, S. S., Weiss, R. S. & Javier, R. T. Binding of human virus oncoproteins to hDLG/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc. Natl Acad. Sci. USA 94, 6670-6675 (1997).
59. Roh, M. H. et al. The Maguk protein, PALS1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost. J. Cell. Biol. 157, 161-172 (2002).
60. Makarova, O., Roh, M. H., Liu, C. J., Laurinec, S. & Margolis, B. Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (PALS1). Gene 302, 21-29 (2003).
61. Straight, S. W. et al. Loss of PALS1 expression leads to tight junction and polarity defects. Mol. Biol. Cell 15, 1981-1990 (2004).
62. Weaver, V. et al. β4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2, 205 (2002). Shows the importance of polarity for tumour cell survival using 3D culture. The formation of polarized 3D structures confers protection from apoptosis in both normal and malignant mammary epithelial cells.
63. Zahir, N. et al. Autocrine laminin-5 ligates α6β4 integrin and activates RAC and NF-κB to mediate anchorage-independent survival of mammary tumors. J. Cell. Biol. 163, 1397-1407 (2003).
64. Debnath, J., Walker, S. J. & Brugge, J. S. AKT activation disrupts mammary acinar architecture and enhances proliferation in an mTOR-dependent manner. J. Cell. Biol. 163, 315-326 (2003).
65. Janda, E., Litos, G., Grunert, S., Downward, J. & Beug, H. Oncogenic RAS/HER2 mediate hyperproliferation of polarized epithelial cells in 3D cultures and rapid tumor growth via the PI3K pathway. Oncogene 21, 5148-5159 (2002).
66. Hotary, K. B. et al. Membrane type I matrix metalloproteinase usurps tumor growth control imposed by the three-dimensional extracellular matrix. Cell 114, 33-45 (2003). Highlights how the remodelling of the ECM by MT1MMP can directly promote the growth and proliferation of cells within a 3D microenvironment.
67. Bissell, M. J. & Radisky, D. Putting tumours in context. Nature Rev. Cancer 1, 46-54 (2001).
68. Egeblad, M. & Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nature Rev. Cancer 2, 161-174 (2002).
69. Hotary, K., Allen, E., Punturieri, A., Yana, I. & Weiss, S. J. Regulation of cell invasion and morphogenesis in a three-dimensional type I collagen matrix by membrane-type matrix metalloproteinases 1, 2, and 3. J. Cell. Biol. 149, 1309-1323 (2000).
70. Moody, S. E. et al. Conditional activation of NEU in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2, 451-461 (2002).
71. Muraoka, R. S. et al. Increased malignancy of NEU-induced mammary tumors overexpressing active transforming growth factor β1. Mol. Cell. Biol. 23, 8691-8703 (2003).
72. Wulf, G., Garg, P., Liou, Y. C., Iglehart, D. & Lu, K. P. Modeling breast cancer in vivo and ex vivo reveals an essential role of PIN1 in tumorigenesis. EMBO J. 23, 3397-3407 (2004).
73. Kacinski, B. M. et al. FMS (CSF1 receptor) and CSF1 transcripts and protein are expressed by human breast carcinomas in vivo and in vitro. Oncogene 6, 941-952 (1991).
74. Becker, K. F. et al. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 54, 3845-3852 (1994).
75. Guilford, P. et al. E-cadherin germline mutations in familial gastric cancer. Nature 392, 402-405 (1998).
76. Kowalski, P. J., Rubin, M. A. & Kleer, C. G. E-cadherin expression in primary carcinomas of the breast and its distant metastases. Breast Cancer Res. 5, R217-R222 (2003).
77. Vivanco, I. & Sawyers, C. L. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nature Rev. Cancer 2, 489-501 (2002).
78. Bjornsti, M. A. & Houghton, P. J. The TOR pathway: a target for cancer therapy. Nature Rev. Cancer 4, 335-348 (2004).
79. Schmelzle, T. & Hall, M. N. TOR, a central controller of cell growth. Cell 103, 253-262 (2000).
80. Majumder, P. K. et al. Prostate intraepithelial neoplasia induced by prostate restricted AKT activation: the MPAKT model. Proc. Natl Acad. Sci. USA 100, 7841-7846 (2003).
81. Majumder, P. K. et al. mTOR inhibition reverses AKT-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nature Med. 10, 594-601 (2004).
82. Friedl, P. & Wolf, K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nature Rev. Cancer 3, 362-374 (2003).
83. Fidler, I. J. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nature Rev. Cancer 3, 453-458 (2003).
84. Liotta, L. A & Stetler-Stevenson, W. G. Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res. 51 (Suppl.), 5054-5059 (1991).
85. Montesano, R., Matsumoto, K., Nakamura, T. & Orci, L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell 67, 901-908 (1991).
86. Lauffenburger, D. A. & Horwitz, A. F. Cell migration: a physically integrated molecular process. Cell 84, 359-369 (1996).
87. Ridley, A. J. et al. Cell migration: integrating signals from front to back. Science 302, 1704-1709 (2003).
88. Niggemann, B. et al. Tumor cell locomotion: differential dynamics of spontaneous and induced migration in a 3D collagen matrix. Exp. Cell Res. 298, 178-187 (2004).
89. Walpita, D. & Hay, E. Studying actin-dependent processes in tissue culture. Nature Rev. Mol. Cell Biol. 3, 137-141 (2002).
90. Friedl, P., Hegerfeldt, Y. & Tusch, M. Collective cell migration in morphogenesis and cancer. Int. J. Dev. Biol. 48, 441-449 (2004).
91. Nabeshima, K. et al. Hepatocyte growth factor/scatter factor induces not only scattering but also cohort migration of human colorectal-adenocarcinoma cells. Int. J. Cancer 78, 750-759 (1998).
92. Yu, W. et al. Hepatocyte growth factor switches orientation of polarity and mode of movement during morphogenesis of multicellular epithelial structures. Mol. Biol. Cell 14, 748-763 (2003).
93. Trelstad, R. L., Hay, E. D. & Revel, J. D. Cell contact during early morphogenesis in the chick embryo. Dev. Biol. 16, 78-106 (1967).
94. Hay, E. D. An overview of epithelio-mesenchymal transformation. Acta Anat. (Basel) 154, 8-20 (1995).
95. Thiery, J. P. Epithelial-mesenchymal transitions in tumour progression. Nature Rev. Cancer 2, 442-454 (2002).
96. Brabletz, T. et al. Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc. Natl Acad. Sci. USA 98, 10356-10361 (2001).
97. Grunert, S., Jechlinger, M. & Beug, H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nature Rev. Mol. Cell Biol. 4, 657-665 (2003).
98. Siegel, P. M. & Massague, J. Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nature Rev. Cancer 3, 807-821 (2003).
99. Dumont, N. & Arteaga, C. L. Targeting the TGFβ signaling network in human neoplasia. Cancer Cell 3, 531-536 (2003).
100. Oft, M. et al. TGF-β1 and HA-RAS collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. 10, 2462-2477 (1996).
101. Janda, E. et al. RAS and TGFβ cooperatively regulate epithelial cell plasticity and metastasis: dissection of RAS signaling pathways. J. Cell. Biol. 156, 299-313 (2002).
102. Lehmann, K. et al. RAF induces TGFβ production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells. Genes Dev. 14, 2610-2622 (2000).
103. Siegel, P. M., Shu, W., Cardiff, R. D., Muller, W. J. & Massague, J. Transforming growth factor β signaling impairs NEU-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc. Natl Acad. Sci. USA 100, 8430-8435 (2003).
104. Seton-Rogers, S. E. et al. Cooperation of the ERBB2 receptor and transforming growth factor β in induction of migration and invasion in mammary epithelial cells. Proc. Natl Acad. Sci. USA 101, 1257-1262 (2004).
105. Lochten A. et al. Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. J. Cell. Biol. 139, 1861-1872 (1997).
106. Soriano, J. V., Pepper, M. S., Nakamura, T., Orci, L. & Montesano, R. Hepatocyte growth factor stimulates extensive development of branching duct-like structures by cloned mammary gland epithelial cells. J. Cell Sci. 108, 413-430 (1995).
107. Pollack, A. L., Runyan, R. B. & Mostov, K. E. Morphogenetic mechanisms of epithelial tubulogenesis: MDCK cell polarity is transiently rearranged without loss of cell-cell contact during scatter factor/hepatocyte growth factor-induced tubulogenesis. Dev. Biol. 204, 64-79 (1998).
108. O'Brien, L. E. et al. ERK and MMPs sequentially regulate distinct stages of epithelial tubule development. Dev. Cell 7, 21-32 (2004). References 107 and 108 provided mechanistic insights into the process of tubulogenesis in 3D collagen cultures, induced by HGF. The transient EMT observed during tubulogenesis might be especially relevant for understanding tumour cell invasion in vivo, where classical EMT is rarely observed.
109. Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L. & Weintraub, H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61, 49-59 (1990).
110. Desprez, P. Y., Hara, E., Bissell, M. J. & Campisi, J. Suppression of mammary epithelial cell differentiation by the helix-loop-helix protein Id-1. Mol. Cell. Biol. 15, 3398-3404 (1995).
111. Desprez, P. Y. et al. A novel pathway for mammary epithelial cell invasion induced by the helix-loop-helix protein Id-1. Mol. Cell. Biol. 18, 4577-4588 (1998).
112. Barsky, S. H. Myoepithelial mRNA expression profiling reveals a common tumor-suppressor phenotype. Exp. Mol. Pathol. 74, 113-122 (2003).
113. Gudjonsson, T. et al. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J. Cell Sci. 115, 39-50 (2002).
114. Runswick, S. K., O'Hare, M. J., Jones, L., Streuli, C. H. & Garrod, D. R. Desmosomal adhesion regulates epithelial morphogenesis and cell positioning. Nature Cell Biol. 3, 823-830 (2001).
115. Bhowmick, N. A et al. TGF-β signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303, 848-851 (2004).
116. Olumi, A. F. et al. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 59, 5002-5011 (1999).
117. Allinen, M. et al. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 6, 17-32 (2004).
118. Parmar, H. et al. A novel method for growing human breast epithelium in vivo using mouse and human mammary fibroblasts. Endocrinology 143, 4886-4896 (2002).
119. Kuperwasser, C. et al. Reconstruction of functionally normal and malignant human breast tissues in mice. Proc. Natl Acad. Sci. USA 101, 4966-4971 (2004).
120. Dixon, J. M. et al. Long-term survivors after breast cancer. Br. J. Surg. 72, 445-448 (1985).
121. Ernster, V. L., Barclay, J., Kerlikowske, K., Grady, D. & Henderson, C. Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA 275, 913-918 (1996).
122. Jaffer, S. & Bleiweiss, I. J. Histologic classification of ductal carcinoma in situ. Microsc. Res. Tech. 59, 92-101 (2002).
123. Page, D. L., Dupont, W. D., Rogers, L. W. & Rados, M. S. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 55, 2698-2708 (1985).
124. Koerner, F. C. Epithelial proliferations of ductal type. Semin. Diagn. Pathol. 21, 10-17 (2004).
125. Burstein, H. J., Polyak, K., Wong, J. S., Lester, S. C. & Kaelin, C. M. Ductal carcinoma in situ of the breast. N. Engl. J. Med. 350, 1430-1441 (2004).
126. Wang, A. Z., Ojakian, G. K. & Nelson, W. J. Steps in the morphogenesis of a polarized epithelium. II. Disassembly and assembly of plasma membrane domains during reversal of epithelial cell polarity in multicellular epithelial (MDCK) cysts. J. Cell Sci. 95, 153-165 (1990).
127. Wang, A. Z., Ojakian, G. K. & Nelson, W. J. Steps in the morphogenesis of a polarized epithelium. I. Uncoupling the roles of cell-cell and cell-substratum contact in establishing plasma membrane polarity in multicellular epithelial (MDCK) cysts. J. Cell Sci. 95, 137-151 (1990).
128. Kleinman, H. K. et al. Basement membrane complexes with biological activity. Biochemistry 25, 312-318 (1986).
129. Niemann, C. et al. Reconstitution of mammary gland development in vitro: requirement of c-met and c-ERBB2 signaling for branching and alveolar morphogenesis. J. Cell. Biol. 143, 533-545 (1998).
130. Roskelley, C. D., Desprez, P. Y. & Bissell, M. J. Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemical signal transduction. Proc. Natl Acad. Sci. USA 91, 12378-12382 (1994).
131. Barcellos-Hoff, M. H., Aggeler, J., Ram, T. G. & Bissell, M. J. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development 105, 223-235 (1989).
132. Emerman, J. T. & Pitelka, D. R. Maintenance and induction of morphological differentiation in dissociated mammary epithelium on floating collagen membranes. In Vitro 13, 316-328 (1977).
133. Emerman, J. T., Bartley, J. C. & Bissell, M. J. Interrelationship of glycogen metabolism and lactose synthesis in mammary epithelial cells of mice. Biochem. J. 192, 695-702 (1980).
134. Wolf, K. et al. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J. Cell. Biol. 160, 267-277 (2003). Illustrates the plasticity of tumour cells when migrating through a 3D microenvironment. On near total pharmacological inhibition of a wide array of proteases, carcinoma cells exhibit a non-proteolytic 'amoeboid' form of cell migration, propulsively squeezing through gaps in the surrounding 3D scaffold.
135. Sahai, E. & Marshal, C. J. Differing modes of tumour cell invasion have distinct requirements for RHO/ROCK signaling and extracellular proteolysis. Nature Cell Biol. 5, 711-719 (2003).
136. Friedl, P. et al. Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. Cancer Res. 55, 4557-4560 (1995).
137. Sakai, T., Larsen, M. & Yamada, K. M. Fibronectin requirement in branching morphogenesis. Nature 423, 876-881 (2003).
138. Nabeshima, K., Inoue, T., Shimao, Y., Kataoka, H. & Koono, M. Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. Histol. Histopathol. 14, 1183-1197 (1999).
139. Mills, K. R., Reginato, M., Debnath, J., Queenan, B. & Brugge, J. S. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro. Proc. Natl Acad. Sci. USA 101, 3438-3443 (2004).
140. Levine, B. & Klionsky, D. J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463-477 (2004).
141. Chambard, M., Verrier, B., Gabrion, J. & Mauchamp, J. Polarity reversal of inside-out thyroid follicles cultured within collagen gel: reexpression of specific functions. Biol. Cell 51, 315-325 (1984).
142. O'Brien, L. E. et al. RAC1 orientates epithelial apical polarity through effects on basolateral laminin assembly. Nature Cell Biol. 3, 831-838 (2001).
143. Yu, W. et al. β1-integrin orients epithelial polarity via RAC1 and laminin. Mol. Biol. Cell 16, 433-445 (2005).
144. Cohen, D. & Musch, A. Apical surface formation in MDCK cells: regulation by the serine/threonine kinase EMK1. Methods 30, 269-276 (2003).
145. Lipschutz, J. H. et al. Exocyst is involved in cystogenesis and tubulogenesis and acts by modulating synthesis and delivery of basolateral plasma membrane and secretory proteins. Mol. Biol. Cell 11, 4259-4275 (2000).