Exclusion from spheroid formation identifies loss of essential cell-cell adhesion molecules in colon cancer cells

Scientific Reports

Volumn 8, Issue 1, 2018, Pages

  Stadler, Mira ^a,c   Scherzer, Martin ^a,b   Walter, Stefanie ^a   Holzner, Silvio ^a   Pudelko, Karoline ^a   Riedl, Angelika ^a,d   Unger, Christine ^a   Kramer, Nina ^a   Weil, Beatrix ^a   Neesen, Jürgen ^a   Hengstschläger, Markus ^a   Dolznig, Helmut ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b KAROLINSKA INSTITUTE   (Sweden)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d BOEHRINGER INGELHEIM RCV GMBH AND CO KG   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; ALPHA CATENIN; CADHERIN; CDH1 PROTEIN, HUMAN; EPCAM PROTEIN, HUMAN; EPITHELIAL CELL ADHESION MOLECULE; LEUKOCYTE ANTIGEN;

CELL ADHESION; CELL COMMUNICATION; CELL MOTION; DEFICIENCY; GENE EXPRESSION REGULATION; GENETICS; HCT 116 CELL LINE; HUMAN; KARYOTYPING; METABOLISM; MULTICELLULAR SPHEROID; PATHOLOGY; PHENOTYPE; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ACTINS; ALPHA CATENIN; ANTIGENS, CD; CADHERINS; CELL ADHESION; CELL COMMUNICATION; CELL LINE, TUMOR; CELL MOVEMENT; EPITHELIAL CELL ADHESION MOLECULE; GENE EXPRESSION REGULATION, NEOPLASTIC; HCT116 CELLS; HUMANS; KARYOTYPING; PHENOTYPE; SIGNAL TRANSDUCTION; SPHEROIDS, CELLULAR;

EID: 85040835064     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-018-19384-0     Document Type: Article

References (55)

1. Kim, J. B. Three-dimensional tissue culture models in cancer biology. Semin Cancer Biol 15, 365-377, https://doi.org/10.1016/j.semcancer.2005.05.002 (2005).
2. Hirschhaeuser, F. et al. Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol 148, 3-15, https://doi.org/10.1016/j.jbiotec.2010.01.012 (2010).
3. Frieboes, H. B. et al. An integrated computational/experimental model of tumor invasion. Cancer Res 66, 1597-1604, https://doi.org/10.1158/0008-5472.CAN-05-3166 (2006).
4. Yamada, K. M. & Cukierman, E. Modeling tissue morphogenesis and cancer in 3D. Cell 130, 601-610, https://doi.org/10.1016/j.cell.2007.08.006 (2007).
5. 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, https://doi.org/10.1083/jcb.200306090 (2004).
6. Streuli, C. H., Bailey, N. & Bissell, M. J. Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity. J Cell Biol 115, 1383-1395 (1991).
7. 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).
8. Friedl, P., Hegerfeldt, Y. & Tusch, M. Collective cell migration in morphogenesis and cancer. Int J Dev Biol 48, 441-449, https://doi.org/10.1387/ijdb.041821 (2004).
9. Amatangelo, M. D., Bassi, D. E., Klein-Szanto, A. J. & Cukierman, E. Stroma-derived three-dimensional matrices are necessary and sufficient to promote desmoplastic differentiation of normal fibroblasts. Am J Pathol 167, 475-488, https://doi.org/10.1016/S0002-9440(10)62991-4 (2005).
10. Desoize, B. & Jardillier, J. Multicellular resistance: a paradigm for clinical resistance? Crit Rev Oncol Hematol 36, 193-207 (2000).
11. van Roy, F. & Berx, G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci 65, 3756-3788, https://doi.org/10.1007/s00018-008-8281-1 (2008).
12. Tsukita, S., Furuse, M. & Itoh, M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2, 285-293, https://doi.org/10.1038/35067088 (2001).
13. Vite, A., Li, J. & Radice, G. L. New functions for alpha-catenins in health and disease: from cancer to heart regeneration. Cell Tissue Res 360, 773-783, https://doi.org/10.1007/s00441-015-2123-x (2015).
14. Yonemura, S., Wada, Y., Watanabe, T., Nagafuchi, A. & Shibata, M. alpha-Catenin as a tension transducer that induces adherens junction development. Nat Cell Biol 12, 533-542, https://doi.org/10.1038/ncb2055 (2010).
15. Schmidt, M., Scholz, C. J., Polednik, C. & Roller, J. Spheroid-based 3-dimensional culture models: Gene expression and functionality in head and neck cancer. Oncol Rep 35, 2431-2440, https://doi.org/10.3892/or.2016.4581 (2016).
16. Pomo, J. M., Taylor, R. M. & Gullapalli, R. R. Influence of TP53 and CDH1 genes in hepatocellular cancer spheroid formation and culture: a model system to understand cancer cell growth mechanics. Cancer Cell Int 16, 44, https://doi.org/10.1186/s12935-016-0318-1 (2016).
17. Lin, R. Z., Chou, L. F., Chien, C. C. & Chang, H. Y. Dynamic analysis of hepatoma spheroid formation: roles of E-cadherin and beta1-integrin. Cell Tissue Res 324, 411-422, https://doi.org/10.1007/s00441-005-0148-2 (2006).
18. Shimazui, T. et al. Role of complex cadherins in cell-cell adhesion evaluated by spheroid formation in renal cell carcinoma cell lines. Oncol Rep 11, 357-360 (2004).
19. Saias, L., Gomes, A., Cazales, M., Ducommun, B. & Lobjois, V. Cell-Cell Adhesion and Cytoskeleton Tension Oppose Each Other in Regulating Tumor Cell Aggregation. Cancer Res 75, 2426-2433, https://doi.org/10.1158/0008-5472.CAN-14-3534 (2015).
20. Watabe, M., Nagafuchi, A., Tsukita, S. & Takeichi, M. Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line. J Cell Biol 127, 247-256 (1994).
21. Ozawa, M. Identification of the region of alpha-catenin that plays an essential role in cadherin-mediated cell adhesion. J Biol Chem 273, 29524-29529 (1998).
22. Maeno, Y. et al. alpha-catenin-deficient F9 cells differentiate into signet ring cells. Am J Pathol 154, 1323-1328 (1999).
23. Capaldo, C. T. & Macara, I. G. Depletion of E-cadherin disrupts establishment but not maintenance of cell junctions in Madin-Darby canine kidney epithelial cells. Mol Biol Cell 18, 189-200, https://doi.org/10.1091/mbc.E06-05-0471 (2007).
24. Cavallaro, U. & Christofori, G. Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough. Biochim Biophys Acta 1552, 39-45 (2001).
25. Cavallaro, U., Schaffhauser, B. & Christofori, G. Cadherins and the tumour progression: is it all in a switch? Cancer Lett 176, 123-128 (2002).
26. Onder, T. T. et al. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res 68, 3645-3654, https://doi.org/10.1158/0008-5472.CAN-07-2938 (2008).
27. Vermeulen, S. J. et al. The alphaE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells. Oncogene 18, 905-915, https://doi.org/10.1038/sj.onc.1202348 (1999).
28. Vermeulen, S. J. et al. Transition from the noninvasive to the invasive phenotype and loss of alpha-catenin in human colon cancer cells. Cancer Res 55, 4722-4728 (1995).
29. Raftopoulos, I., Davaris, P., Karatzas, G., Karayannacos, P. & Kouraklis, G. Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival. J Surg Oncol 68, 92-99 (1998).
30. Van Marck, V., Stove, C., Jacobs, K., Van den Eynden, G. & Bracke, M. P-cadherin in adhesion and invasion: opposite roles in colon and bladder carcinoma. Int J Cancer 128, 1031-1044, https://doi.org/10.1002/ijc.25427 (2011).
31. Bujko, M. et al. Expression changes of cell-cell adhesion-related genes in colorectal tumors. Oncol Lett 9, 2463-2470, https://doi.org/10.3892/ol.2015.3107 (2015).
32. Paredes, J. et al. P-cadherin is up-regulated by the antiestrogen ICI 182,780 and promotes invasion of human breast cancer cells. Cancer Res 64, 8309-8317, https://doi.org/10.1158/0008-5472.CAN-04-0795 (2004).
33. Ben Hamida, A. et al. Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: prominent expression of P-cadherin. BMC Cancer 8, 28, https://doi.org/10.1186/1471-2407-8-28 (2008).
34. Taniuchi, K. et al. Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer Res 65, 3092-3099, https://doi.org/10.1158/0008.5472.CAN-04-3646 (2005).
35. Cheung, L. W. et al. P-cadherin cooperates with insulin-like growth factor-1 receptor to promote metastatic signaling of gonadotropin-releasing hormone in ovarian cancer via p120 catenin. Oncogene 30, 2964-2974, https://doi.org/10.1038/onc.2011.7 (2011).
36. Van Marck, V. et al. P-cadherin promotes cell-cell adhesion and counteracts invasion in human melanoma. Cancer Res 65, 8774-8783, https://doi.org/10.1158/0008-5472.CAN-04-4414 (2005).
37. Sarrio, D. et al. Functional characterization of E- and P-cadherin in invasive breast cancer cells. BMC Cancer 9, 74, https://doi.org/10.1186/1471-2407-9-74 (2009).
38. Bauer, K., Dowejko, A., Bosserhoff, A. K., Reichert, T. E. & Bauer, R. J. P-cadherin induces an epithelial-like phenotype in oral squamous cell carcinoma by GSK-3beta-mediated Snail phosphorylation. Carcinogenesis 30, 1781-1788, https://doi.org/10.1093/carcin/bgp175 (2009).
39. Ribeiro, A. S. et al. P-cadherin functional role is dependent on E-cadherin cellular context: a proof of concept using the breast cancer model. J Pathol 229, 705-718, https://doi.org/10.1002/path.4143 (2013).
40. Ozawa, M. & Kemler, R. Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex. J Biol Chem 273, 6166-6170 (1998).
41. Imamura, Y., Itoh, M., Maeno, Y., Tsukita, S. & Nagafuchi, A. Functional domains of alpha-catenin required for the strong state of cadherin-based cell adhesion. J Cell Biol 144, 1311-1322 (1999).
42. van Roy, F. Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer 14, 121-134, https://doi.org/10.1038/nrc3647 (2014).
43. Walzl, A. et al. The Resazurin Reduction Assay Can Distinguish Cytotoxic from Cytostatic Compounds in Spheroid Screening Assays. J Biomol Screen 19, 1047-1059, https://doi.org/10.1177/1087057114532352 (2014).
44. Cheung, K. J., Gabrielson, E., Werb, Z. & Ewald, A. J. Collective invasion in breast cancer requires a conserved basal epithelial program. Cell 155, 1639-1651, https://doi.org/10.1016/j.cell.2013.11.029 (2013).
45. Prasetyanti, P. R. et al. Regulation of stem cell self-renewal and differentiation by Wnt and Notch are conserved throughout the adenoma-carcinoma sequence in the colon. Molecular cancer 12, 126, https://doi.org/10.1186/1476-4598-12-126 (2013).
46. Efstathiou, J. A. et al. Mutated epithelial cadherin is associated with increased tumorigenicity and loss of adhesion and of responsiveness to the motogenic trefoil factor 2 in colon carcinoma cells. Proc Natl Acad Sci USA 96, 2316-2321 (1999).
47. Tym, J. E. et al. canSAR: an updated cancer research and drug discovery knowledgebase. Nucleic Acids Res 44, D938-943, https://doi.org/10.1093/nar/gkv1030 (2016).
48. Tay, P. N. et al. Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells. Int J Oncol 37, 909-926 (2010).
49. Zhang, C. C. et al. PF-03732010: a fully human monoclonal antibody against P-cadherin with antitumor and antimetastatic activity. Clin Cancer Res 16, 5177-5188, https://doi.org/10.1158/1078-0432.CCR-10-1343 (2010).
50. Matsubara, S. & Ozawa, M. Expression of alpha-catenin in alpha-catenin-deficient cells results in a reduced proliferation in three-dimensional multicellular spheroids but not in two-dimensional monolayer cultures. Oncogene 23, 2694-2702, https://doi.org/10.1038/sj.onc.1207423 (2004).
51. Vermeulen, S. J. et al. Did the four human cancer cell lines DLD-1, HCT-15, HCT-8, and HRT-18 originate from one and the same patient? Cancer Genet Cytogenet 107, 76-79 (1998).
52. Medico, E. et al. The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets. Nat Commun 6, 7002, https://doi.org/10.1038/ncomms8002 (2015).
53. Korff, T. & Augustin, H. G. Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation. J Cell Biol 143, 1341-1352 (1998).
54. Weiswald, L. B. et al. In situ protein expression in tumour spheres: development of an immunostaining protocol for confocal microscopy. BMC Cancer 10, 106, https://doi.org/10.1186/1471-2407-10-106 (2010).
55. Dolznig, H. et al. Modeling colon adenocarcinomas in vitro a 3D co-culture system induces cancer-relevant pathways upon tumor cell and stromal fibroblast interaction. Am J Pathol 179, 487-501, https://doi.org/10.1016/j.ajpath.2011.03.015 (2011).