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Comparative analysis of colorectal carcinoma cell lines that differ in metastatic potential

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Abstract

The present work is an attempt to compare cancer cells of the same origin but differing in the expression of CEA protein, a clinical marker of metastatic carcinomas. CEA, presumably, is one of the key factors in metastatic activity. We investigated the morphology of cell colonies in vitro, the expression pattern of epithelial markers, and the ability of these cells to form tumors and metastases in vivo. Their stem component was evaluated with a suicidal genetic construct sensitive to Oct4, an embryonic stem cell marker.

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Abbreviations

RT-PCR:

reverse transcription polymerase chain reaction

CEA:

carcinoembryonic antigen

PBS:

phosphate buffered saline

References

  • Bajenova, O., Stolper, E., Gapon, S., Sundina, N., Zimmer, R., and Thomas, P., Surface expression of heterogeneous nuclear RNA binding protein M4 on Kupffer cell relates to its function as a carcinoembryonic antigen receptor Exp. Cell Res., 2003, vol. 291, pp. 228–241.

    Article  PubMed  CAS  Google Scholar 

  • Bajenova, O., Chaika, N., and Thomas, P.., Carcinoembryonic antigen promotes metastasis via disruption of E-cadherin adherens junction complexes, in 14th International Biennial Congress of the Metastasis Research Society, September 2012, Brisbane, Australia, 2012, no. 96.

    Google Scholar 

  • Ballantyne, G.H., and Quin, J., Surgical treatment of liver metastases in patients with colorectal cancer, Cancer, 1993, vol. 71, pp. 4252–4266.

    Article  PubMed  CAS  Google Scholar 

  • Berinstein, N.L., Carcinoembrionic antigen as a target for therapeutic anticancer vaccines: a review, J. Clin. Oncol., 2002, vol. 200220, pp. 2197–2207.

    Article  Google Scholar 

  • Blumenthal, R.D., Hansen, H.J., and Goldenberg, D.M., Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen), Cancer Res., 2005a, vol. 65, pp. 8809–8817.

    Article  PubMed  CAS  Google Scholar 

  • Blumenthal, R.D., Osorio, L., Hayes, M.K., Horak, I.D., Hansen, H.J., and Goldenberg, D.M., Carcinoembryonic antigen antibody inhibits lung metastasis and augments chemotherapy in a human colonic carcinoma xenograft, Cancer Immunol. Immunother., 2005b, vol. 54, pp. 315–327.

    Article  PubMed  CAS  Google Scholar 

  • Brembreck, F.H., Rosario, M., and Birchmeier, W., Balancing cell adhesion and Wnt signaling, the key role ofcatenin, Curr. Opin. Genet. Dev., 2006, vol. 16, pp. 51–59.

    Article  Google Scholar 

  • Camacho-Leal, P., and Stanners, C.P., The human carcinoembryonic antigen (CEA) GPI anchor mediates anoikis inhibition by inactivation of the intrinsic death pathway, Oncogene, 2008, vol. 27, pp. 1545–1553.

    Article  PubMed  CAS  Google Scholar 

  • Davydov-Sinitsyn, A.P., Bajenova, O.V., Liskovykh, M.A., Chechik, L.L., Ponomartsev, S.V., Tomilin, A.N., and Tolkunova, E.N., In vitro derivation and characterization of a colorectal cancer stem cell subpopulation, Cell Tiss. Biol., 2013, vol. 7 (in press).

  • Duxbury, M.S., Ito, H., Zinner, M.J., Ashley, S.W., and Whang, E.E., CEACAM6 gene silencing impairs anoikis resistance and in vivo metastatic ability of pancreatic adenocarcinoma cells, Oncogene, 2004, vol. 23, pp. 465–473.

    Article  PubMed  CAS  Google Scholar 

  • Eidelman, F.J., Fuks, A., DeMarte, L., Taheri, M., and Stanners, C.P., Human carcinoembryonic antigen, an intercellular adhesion molecule, blocks fusion and differentiation of rat myoblasts, J. Cell. Biol., 1993, vol. 123, pp. 467–475.

    Article  PubMed  CAS  Google Scholar 

  • Fiorentino, F., Hunt, I., Teoh, K., Treasure, T., and Utley, M., Pulmonary metastasectomy in colorectal cancer: a systematic review and quantitative synthesis, J. R. Soc. Med., 2010, vol. 103, pp. 60–66.

    Article  PubMed  Google Scholar 

  • Fodde, R. and Brabletz, T., Wnt/beta-catenin signaling in cancer stemness and malignant behavior, Curr. Opin. Biol., 2007, vol. 19, pp. 150–158.

    Article  CAS  Google Scholar 

  • Fusai, G. and Davidson, B.R., Management of colorectal liver metastases, Colorectal Dis., 2003, vol. 5, pp. 2–23.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, M.J. and Mitchell, E.P., Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer, Cancer Invest., 2005, vol. 23, pp. 338–351.

    Article  PubMed  Google Scholar 

  • Goya, T., Miyazawa, N., Kondo, H., Tsuchiya, R., Naruke, T, and Suemasu, K., Surgical resection of pulmonary metastases from colorectal cancer: 10-year follow-up, Cancer, 1989, vol. 64, pp. 1418–1421.

    Article  PubMed  CAS  Google Scholar 

  • Hoffmeyer, K., Raggioli, A., Rudolff, S., Anton, R., Heirholzer, A., Del, Valle, I., Herin, K., Vogt, R., and Kemler, R., Wnt/-catenin signaling regulates telomerase in stem cells and cancer cells, Science, 2012, vol. 336, pp. 1549–1554.

    Article  PubMed  CAS  Google Scholar 

  • Hostetter, R.B., Augustus, L.B., and Mankarious, R., Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis, J. Natl. Cancer. Inst., 1990, vol. 82, pp. 380–385.

    Article  PubMed  CAS  Google Scholar 

  • Huerta, S., Recent advances in the molecular diagnosis and prognosis of colorectal cancer, Expert Rev. Mol. Diagn., 2008, vol. 8, pp. 277–288.

    Article  PubMed  CAS  Google Scholar 

  • Jessup, J.M. and Thomas, P., CEA and metastasis: a facilitator of site-specific metastasis, in Cell Adhesion and Communication Mediated by the CEA Family: Basic and Clinical Perspectives, New York: CRC Press, 1998, pp. 195–222.

    Google Scholar 

  • Knychialski, B. and Lukienzuk, T., The evaluation of diagnostic value of the tumor markers: CCSA-2 and CEA in colorectal cancer, Pol. Przegl. Chir., 2012, vol. 201282, pp. 86–92.

    Google Scholar 

  • Laguinge, L., Bajenova, O., Bowden, E., Sayyah, J., Thomas, P., and Juhl, H., Surface expression and CEA binding of HnRNP M4 protein in HT29 colon cancer cells, Anticancer Res., 2005, vol. 200525, pp. 23–31.

    Google Scholar 

  • Le, N.H., Franken, P., and Fodde, R., Tumor-stroma interactions in colorectal cancer: converging on Beta-catenin activation and cancer stemness, Br. J. Cancer., 2008, vol. 98, pp. 1886–1893.

    Article  PubMed  CAS  Google Scholar 

  • Lee, W.S., Baek, J.H., Kim, K.K., and Park, Y.H., The prognostic significant of percentage drop in serum CEA post curative resection for colon cancer, Surg. Oncol., 2012, vol. 21, pp. 45–51.

    Article  PubMed  Google Scholar 

  • Li, F., Tiede, B., Massague, J., and Kang, Y., Beyond tumorigenesis: cancer stem cells in metastasis, Cell Res., 2007, vol. 17, pp. 3–14.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y., Cao, H., Jiao, Z., Pakala, S.B., Sirigirl, D.N.R., Li, W., Kumar, R., and Mishra, L., Carcinoembrionic antigen interacts with TGF-β receptor and inhibits TGF-β signaling in colorectal cancers, Cancer Res., 2010, vol. 70, pp. 8159–8168.

    Article  PubMed  CAS  Google Scholar 

  • Liotta, L.A., Tumor invasion and metastases: role of basement membrane. Warner-Lambert Parke-Davis Award lecture, Am. J. Pathol., 1984, vol. 117, pp. 339–348.

    PubMed  CAS  Google Scholar 

  • Liskovykh, M.A., Chuikin, I.A., Ranyan, A., Safina, D.A., Tolkunova, E.N., Minina, Yu.M., Zhdanova, N.S., Dyban, P.A., Mullins, J., Kostyleva, E.I., Chikhirzhina, E.V., Bader, M., Alenina, N., and Tomilin, A.N., Generation of rat induced pluripotent stem cells: the analysis of reprogramming and culturing media, Tsitologiia, 2011, 2011, vol. 53, no. 12, pp. 939–945.

    PubMed  CAS  Google Scholar 

  • Marotta, L.L. and Polyak, K., Cancer stem cells: a model in the making, Curr. Opin. Genet. Dev., 2009, vol. 19, pp. 44–50.

    Article  PubMed  Google Scholar 

  • Mourtzikou, A., Stamouli, M., Kroupis, C., Christodoulou, S., Skondra, M., Kastania, A., Pestasides, D., Athanases, G., and Dimas, C., Evaluation of carcinoembryonic (CEA), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule EpCAM (GA733-2), and carbohydrate antigen 19-9 (CA 19-9) levels in colorectal cancer patients and correlation with clinicopathological characteristics, Clin. Lab., 2012, vol. 58, pp. 441–448.

    PubMed  CAS  Google Scholar 

  • O’Brien, C.A., Kreso, A., and Dick, J.E., Cancer stem cells in solid tumors: an overview, Semin. Radiat. Oncol., 2009, vol. 19, pp. 71–77.

    Article  PubMed  Google Scholar 

  • O’Reilly, D.A. and Poston, G.J., Colorectal liver metastases: current and future perspectives, Future Oncol., 2006, vol. 2, pp. 525–531.

    Article  PubMed  Google Scholar 

  • Ordoñez, C., Screaton, R.A., Ilantzis, C., and Stanners, C.P., Human carcinoembryonic antigen functions as a general inhibitor of anoikis, Cancer Res., 2000, vol. 200060, pp. 3419–3424.

    Google Scholar 

  • Perez, L., Ayala, M., Pimentel, G., Bell, H., Canaan-Haden, L., Bequet, M., Gonzalez, L.J., Miranda, M., Ravelo, R., Roque, L., Acevedo, B., Oliva, J.P., and Gavilondo, J.V., A Multivalent recombinant antibody fragment specific for carcinoembryonic antigen, Biotechnol. Appl. Biochem., 2006, vol. 43, pp. 39–48.

    Article  PubMed  CAS  Google Scholar 

  • Rao, U.S., Hoerster, N.S., Thirumala, S., and Rao, P.S., The influence of metastatic site on the expression of CEA and cellular localization of β-catenin in colorectal cancer, J. Gastroenterol. Hepatol. 2012 (in press).

    Google Scholar 

  • Reya, N., Morrison, S.J., Clarke, M.F., and Weissman, I.L., Stem cells, cancer, and cancer stem cells, Nature, 2001, vol. 414, pp. 101–111.

    Article  Google Scholar 

  • Rotolo, N., De, Monte, L., Imperatori, A., and Dominioni, L., Pulmonary resections of single metastases from colorectal cancer, Surg. Oncol., 2007, vol. 16,suppl. 1, pp. S141–S144.

    Article  PubMed  Google Scholar 

  • Samara, R.N., Laguinge, L.M., and Jessup, J.M., Carcinoembryonic antigen inhibits anoikis in colorectal carcinoma cells by interfering with TRAIL-R2 (DR5) signaling, Cancer Res., 2007, vol. 67, pp. 4774–4782.

    Article  PubMed  CAS  Google Scholar 

  • Screaton, R.A., DeMarte, L., Draber, P., and Stanners, C.P., The specificity for the differentiation blocking activity of carcinoembryonic antigen resides in its glycophosphatidyl-inositol anchor, J. Cell. Biol., 2000, vol. 150, pp. 613–626.

    Article  PubMed  CAS  Google Scholar 

  • Screaton, R.A., Penn, L.Z., and Stanners, C.P., Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation, J. Cell. Biol., 1997, vol. 19;137, pp. 939–52.

    Article  Google Scholar 

  • Soeth, E., Wirth, T., List, H.J., Kumbhani, S., Petersen, A., Neumaler, M., Czubayko, F., and Juhl, H., Controlled ribozyme targeting demonstrates an antiapoptotic effect of carcinoembryonic antigen in HT29 colon cancer cells, Clin. Cancer Res., 2001, vol. 7, pp. 2022–2030.

    PubMed  CAS  Google Scholar 

  • Sreekumar, R., Sayan, B.S., Mimezami, A.H., and Sayan, A.E., MicroRNA control of invasion and metastasis pathways, Front. Genet., 2011, vol. 2, p. 58.

    Article  PubMed  Google Scholar 

  • Taheri, M., Saragovi, H.U., and Stanners, C.P., The adhesion and differentiation-inhibitory activities of the immunoglobulin superfamily member, carcinoembryonic antigen, can be independently blocked, J. Biol. Chem., 2003, vol. 278, pp. 14632–14639.

    Article  PubMed  CAS  Google Scholar 

  • Tan, E., Gouvas, N., Nicholls, R.J., Ziprin, P., Xynos, E., and Tekkis, P.P., Diagnostic precision of carcinoembryonic antigen in the detection of recurrence of colorectal cancer, Surg. Oncol., 2009, vol. 18, pp. 15–24.

    Article  PubMed  Google Scholar 

  • Thomas, P., Forse, R.A., and Bajenova, O., Carcinoembryonic antigen (CEA) and its receptor HnRNP M are mediators of metastasis and the inflammatory response in the liver, Clin. Exp. Metastasis, 2011, vol. 28, pp. 923–932.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, P., Gangopadhyay, A., Steele, G.Jr., Andrews, C., Nakazato, H., Oikawa, S., and Jessup, J.M., The effect of transfection of the CEA gene on the metastatic behavior of the human colorectal cancer cell line MIP-101, Cancer Lett., 1995, vol. 92, pp. 59–66.

    Article  PubMed  CAS  Google Scholar 

  • Uchino, J., Takayama, K., Harada, A., Sone, T., Harada, T., Curiel, D.T., Kuroki, M., and Nakanishi, Y., Tumor targeting carboxylesterase fused with anti-CEA scFv improve the anticancer effect with a less toxic dose of irinotecan, Cancer Gene Ther., 2008, vol. 15, pp. 94–100.

    Article  PubMed  CAS  Google Scholar 

  • Wagner, H.E., Toth, C.A., Steele, G.D.Jr., and Thomas, P., Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production, Clin. Exp. Metastasis, 1992, vol. 10, pp. 25–31.

    Article  PubMed  CAS  Google Scholar 

  • Yeung, T.M., Gandhi, S.C., Wilding, J.L, Muschel, R., and Bodmer, W.F., Cancer stem cells from colorectal cancerderived cell lines, Proc. Natl. Acad. Sci. USA., 2010, vol. 107, pp. 3722–3727.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to A. P. Davydov-Sinitsyn.

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Original Russian Text © A.P. Davydov-Sinitsyn, O.V. Bajenova, M.A. Liskovykh, S.V. Ponomartsev, L.L. Chechik, A.N. Tomilin, E.N. Tolkunova, 2013, published in Tsitologiya, 2013, Vol. 55, No. 6, pp. 379–387.

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Davydov-Sinitsyn, A.P., Bajenova, O.V., Liskovykh, M.A. et al. Comparative analysis of colorectal carcinoma cell lines that differ in metastatic potential. Cell Tiss. Biol. 7, 407–416 (2013). https://doi.org/10.1134/S1990519X13050040

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