Carcinoembryonic Antigen: a Multifunctional Molecule in Colorectal Cancer Progression and Metastasis

Main Article Content

Peter Thomas Murali Kuracha Brian Loggie Venkatesh Govindarajan

Abstract

Abstract

Colorectal cancer is a major public health problem and the majority of deaths associated with the disease are the result of metastatic spread to the liver. The biology of colorectal cancer metastasis is slowly being unraveled and involves multiple mechanisms that provide the cancer cell with an advantage for invasion, survival in the circulation and for implantation and growth in the liver. A glycoprotein tumor product that seems to offer an advantage in all these areas is carcinoembryonic antigen (CEA, CEACAM5, CD66e). While the function of CEA in normal tissues is still a subject of speculation, CEA seems to play a critical role in cancer and is involved in multiple mechanisms that are designed to provide the cancer cell with an advantage to invade and metastasize. These mechanisms include induction of changes in the tumor microenvironment at both the primary and distant metastatic site, protection against both apoptosis and cytotoxicity and implementation of angiogenisis. Thus, this review is focused on the role of CEA in promoting colorectal cancer progression and metastasis especially to the liver.

 

Keywords: carcinoembryonic antigen; liver metastasis, colorectal cancer, anoikis, angiogenesis, cytokines

Article Details

How to Cite
THOMAS, Peter et al. Carcinoembryonic Antigen: a Multifunctional Molecule in Colorectal Cancer Progression and Metastasis. Medical Research Archives, [S.l.], v. 5, n. 3, mar. 2017. ISSN 2375-1924. Available at: <https://journals.ke-i.org/mra/article/view/1120>. Date accessed: 04 aug. 2020.
Keywords
Keywords: carcinoembryonic antigen; liver metastasis, colorectal cancer, anoikis, angiogenesis, cytokines
Section
Review Articles

References

Aarons, C.B., Bajenova, O., Andrews, C., Heydrick, S., Bushell, K.N., Reed, K.L., Thomas, P., Becker, J.M. and Stucchi, A.F., 2007. Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell–cell adhesion of colorectal cancer cells. Clinical & experimental metastasis, 24(3), pp.201-209.

Adson, M.A., 1987. Resection of liver metastases—when is it worthwhile? World journal of surgery, 11(4), pp.511-520.

André, T., Boni, C., Mounedji-Boudiaf, L., Navarro, M., Tabernero, J., Hickish, T., Topham, C., Zaninelli, M., Clingan, P., Bridgewater, J. and Tabah-Fisch, I., 2004. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. New England Journal of Medicine, 350(23), pp.2343-2351.

Arnaud, J.P., Koehl, C. and Adloff, M., 1980. Carcinoembryonic antigen (CEA) in diagnosis and prognosis of colorectal carcinoma. Diseases of the Colon & Rectum, 23(3), pp.141-144.

Bacac, M., Fauti, T., Sam, J., Colombetti, S., Weinzierl, T., Ouaret, D., Bodmer, W., Lehmann, S., Hofer, T., Hosse, R.J. and Moessner, E., 2016. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. Clinical Cancer Research, 22(13), pp.3286-3297.

Baum, B., Settleman, J. and Quinlan, M.P., 2008, June. Transitions between epithelial and mesenchymal states in development and disease. In Seminars in cell & developmental biology (Vol. 19, No. 3, pp. 294-308). Academic Press.

Bajenova, O., Chaika, N., Tolkunova, E., Davydov-Sinitsyn, A., Gapon, S., Thomas, P. and O’Brien, S., 2014. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes. Experimental cell research, 324(2), pp.115-123.

Bajenova, O., Gorbunova, A., Evsyukov, I., Rayko, M., Gapon, S., Bozhokina, E., Shishkin, A. and O’Brien, S.J., 2016. The Genome-Wide Analysis of Carcinoembryonic Antigen Signaling by Colorectal Cancer Cells Using RNA Sequencing. PloS one, 11(9), p.e0161256.

Bajenova, O., Stolper, E., Gapon, S., Sundina, N., Zimmer, R. and Thomas, P., 2003. Surface expression of heterogeneous nuclear RNA binding protein M4 on Kupffer cell relates to its function as a carcinoembryonic antigen receptor. Experimental cell research, 291(1), pp.228-241\

Bajenova, O.V., Zimmer, R., Stolper, E., Salisbury-Rowswell, J., Nanji, A. and Thomas, P., 2001. Heterogeneous RNA-binding protein M4 is a receptor for carcinoembryonic antigen in Kupffer cells. Journal of Biological Chemistry, 276(33), pp.31067-31073.

Beauchemin, N. and Arabzadeh, A., 2013. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer and Metastasis Reviews, 32(3-4), pp.643-671.

Beauchemin N, Draber P, Dveksler G, Gold P, Gray-Owen S, Grunert F, Hammarström S, Holmes KV, Karlsson A, Kuroki M, Lin SH et al.. Redefined nomenclature for members of the carcinoembryonic antigen family. Experimental cell research. 1999 Nov 1; 252(2):243.

Behr, T.M., Sharkey, R.M., Juweid, M.I., Dunn, R.M., Ying, Z., Zhang, C.H., Siegel, J.A., Gold, D.V. and Goldenberg, D.M., 1996. Factors influencing the pharmacokinetics, dosimetry, and diagnostic accuracy of radioimmunodetection and radioimmunotherapy of carcinoembryonic antigen-expressing tumors. Cancer research, 56(8), pp.1805-1816.

Benchimol, S., Fuks, A., Jothy, S., Beauchemin, N., Shirota, K. and Stanners, C.P., 1989. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell, 57(2), pp.327-334.

Bramswig, K.H., Poettler, M., Unseld, M., Wrba, F., Uhrin, P., Zimmermann, W., Zielinski, C.C. and Prager, G.W., 2013. Soluble carcinoembryonic antigen activates endothelial cells and tumor angiogenesis. Cancer research, 73(22), pp.6584-6596.

Bengtsson, G., Carlsson, G., Hafström, L. and Jönsson, P.E., 1981. Natural history of patients with untreated liver metastases from colorectal cancer. The American Journal of Surgery, 141(5), pp.586-589.

Boffetta, P., Hashibe, M., La Vecchia, C., Zatonski, W. and Rehm, J., 2006. The burden of cancer attributable to alcohol drinking. international Journal of Cancer, 119(4), pp.884-887.

Camacho-Leal, P. and Stanners, C.P., 2008. The human carcinoembryonic antigen (CEA) GPI anchor mediates anoikis inhibition by inactivation of the intrinsic death pathway. Oncogene, 27(11), pp.1545-1553.

Canbay, E., Ishibashi, H., Sako, S., Mizumoto, A., Hirano, M., Ichinose, M., Takao, N. and Yonemura, Y., 2013. Preoperative carcinoembryonic antigen level predicts prognosis in patients with Pseudomyxoma Peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World journal of surgery, 37(6), pp.1271-1276.

Chandrasekaran, E.V., Davila, M., Nixon, D.W., Goldfarb, M. and Mendicino, J., 1983. Isolation and structures of the oligosaccharide units of carcinoembryonic antigen. Journal of Biological Chemistry, 258(11), pp.7213-7222.


Chen, J., Raju, G.S., Jogunoori, W., Menon, V., Majumdar, A., Chen, J.S., Gi, Y.J., Jeong, Y.S., Phan, L., Belkin, M. and Gu, S., 2016. Mutational Profiles Reveal an Aberrant TGF-β-CEA Regulated Pathway in Colon Adenomas. PloS one, 11(4), p.e0153933.

Chen, S., Zhang, J., Duan, L., Zhang, Y., Li, C., Liu, D., Ouyang, C., Lu, F. and Liu, X., 2013. Identification of HnRNP M as a Novel Biomarker for Colorectal Carcinoma by Quantitative Proteomics. American Journal of Physiology-Gastrointestinal and Liver Physiology.

Dhar, P., Moore, T., Zamcheck, N. and Kupchik, H.Z., 1972. Carcinoembryonic antigen (CEA) in colonic cancer: Use in preoperative and postoperative diagnosis and prognosis. Jama, 221(1), pp.31-35.

Daneker, G.W., Piazza, A.J., Steele, G.D. and Mercurio, A.M., 1989. Relationship between extracellular matrix interactions and degree of differentiation in human colon carcinoma cell lines. Cancer research, 49(3), pp.681-686.

Datar, K.V., Dreyfuss, G. and Swanson, M.S., 1993. The human hnRNP M proteins: identification of a methionine/arginine-rich repeat motif in ribonucleoproteins. Nucleic acids research, 21(3), pp.439-446.

Duffy, M.J., 2001. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful?. Clinical chemistry, 47(4), pp.624-630.

Edge, S.B., 2010. American Cancer Society. AJCC cancer staging handbook: from the AJCC cancer staging manual.

Fong, Y., Kemeny, N., Paty, P., Blumgart, L.H. and Cohen, A.M., 1996, July. Treatment of colorectal cancer: hepatic metastasis. In Seminars in surgical oncology (Vol. 12, No. 4, pp. 219-252). John Wiley & Sons, Inc..

Fortner, J.G., Silva, J.S., Golbey, R.B., Cox, E.B. and Maclean, B.J., 1984. Multivariate analysis of a personal series of 247 consecutive patients with liver metastases from colorectal cancer. I. Treatment by hepatic resection. Annals of surgery, 199(3), p.306.

Gangopadhyay, A., Bajenova, O., Kelly, T.M. and Thomas, P., 1996. Carcinoembryonic antigen induces cytokine expression in Kupffer cells: implications for hepatic metastasis from colorectal cancer. Cancer research, 56(20), pp.4805-4810.

Gangopadhyay, A., Lazure, D.A. and Thomas, P., 1998. Adhesion of colorectal carcinoma cells to the endothelium is mediated by cytokines from CEA stimulated Kupffer cells. Clinical & experimental metastasis, 16(8), pp.703-712.

Gold, P. and Freedman, S.O., 1965. Specific carcinoembryonic antigens of the human digestive system. Journal of Experimental Medicine, 122(3), pp.467-481.

Goldstein, M.J. and Mitchell, E.P., 2005. Carcinoembryonic antigen in the staging and follow-up of patients with colorectal cancer. Cancer investigation, 23(4), pp.338-351.

Goldenberg, D.M., Kim, E.E., DeLand, F.H., Bennett, S. and Primus, F.J., 1980. Radioimmunodetection of cancer with radioactive antibodies to carcinoembryonic antigen. Cancer Research, 40(8 Part 2), pp.2984-2992.

Greenburg, G. and Hay, E.D., 1982. Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells. The Journal of cell biology, 95(1), pp.333-339.

Hammarström, S., 1999, April. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. In Seminars in cancer biology (Vol. 9, No. 2, pp. 67-81). Academic Press.

Han, S.U., Kwak, T.H., Her, K.H., Cho, Y.H., Choi, C., Lee, H.J., Hong, S., Park, Y.S., Kim, Y.S., Kim, T.A. and Kim, S.J., 2008. CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling. Oncogene, 27(5), pp.675-683.

Hashino, J., Fukuda, Y., Oikawa, S., Nakazato, H. and Nakanishi, T., 1994. Metastatic potential of human colorectal carcinoma SW1222 cells transfected with cDNA encoding carcinoembryonic antigen. Clinical & experimental metastasis, 12(4), pp.324-328.

Hostetter, R.B., Augustus, L.B., Mankarious, R., Chi, K., Fan, D., Toth, C., Thomas, P. and Jessup, J.M., 1990. Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. Journal of the National Cancer Institute, 82(5), pp.380-385.

Hughes, K. S., et al. "Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence." Surgery 100.2 (1986): 278-284.

Hugo, H., Ackland, M.L., Blick, T., Lawrence, M.G., Clements, J.A., Williams, E.D. and Thompson, E.W., 2007. Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression. Journal of cellular physiology, 213(2), pp.374-383.

Iddings, D. and Bilchik, A., 2007. The biologic significance of micrometastatic disease and sentinel lymph node technology on colorectal cancer. Journal of surgical oncology, 96(8), pp.671-677.

Jensen-Jarolim, E., Fazekas, J., Singer, J., Hofstetter, G., Oida, K., Matsuda, H. and Tanaka, A., 2015. Crosstalk of carcinoembryonic antigen and transforming growth factor-β via their receptors: comparing human and canine cancer. Cancer Immunology, Immunotherapy, 64(5), pp.531-537.

Jessup, J.M., Giavazzi, R., Campbell, D., Cleary, K., Morikawa, K. and Fidler, I.J., 1988. Growth potential of human colorectal carcinomas in nude mice: association with the preoperative serum concentration of carcinoembryonic antigen in patients. Cancer research, 48(6), pp.1689-1692.

Jessup, J.M., Giavazzi, R., Campbell, D., Cleary, K.R., Morikawa, K., Hostetter, R., Atkinson, E.N. and Fidler, I.J., 1989. Metastatic potential of human colorectal carcinomas implanted into nude mice: prediction of clinical outcome in patients operated upon for cure. Cancer research, 49(24 Part 1), pp.6906-6910.

Jessup, J.M., Laguinge, L., Lin, S., Samara, R., Aufman, K., Battle, P., Frantz, M., Edmiston, K.H. and Thomas, P., 2004. Carcinoembryonic antigen induction of IL‐10 and IL‐6 inhibits hepatic ischemic/reperfusion injury to colorectal carcinoma cells. International journal of cancer, 111(3), pp.332-337.

Jessup, J.M., Samara, R., Battle, P. and Laguinge, L.M., 2005. Carcinoembryonic antigen promotes tumor cell survival in liver through an IL-10-dependent pathway. Clinical & experimental metastasis, 21(8), pp.709-717.

Jessup, J.M. and Thomas, P., 1998. CEA and metastasis: a facilitator of site-specific metastasis. Cell Adhesion and Communications Mediated by the CEA Family, 5, pp.195-222.

Jessup, M. and Thomas, P., 1989. Carcinoembryonic antigen: function in metastasis by human colorectal carcinoma. Cancer and Metastasis Reviews, 8(3), pp.263-280.

Kaufman, H., Schlom, J. and Kantor, J., 1991. A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA). International journal of cancer, 48(6), pp.900-907.

Kemeny, M.M., Goldberg, D., Beatty, J.D., Blayney, D., Browning, S., Doroshow, J., Ganteaume, L., Hill, R.L., Kokal, W.A., Riihimaki, D.U. and Terz, J.J., 1986. Results of a prospective randomized trial of continuous regional chemotherapy and hepatic resection as treatment of hepatic metastases from colorectal primaries. Cancer, 57(3), pp.492-498.

Kemeny, N.E. and Schneider, A.M., 1989. Regional treatment of hepatic metastases and hepatocellular carcinoma. Current problems in cancer, 13(4), pp.203-283.

Kuracha, M.R., Thomas, P., Loggie, B.W. and Govindarajan, V., 2016. Patient‐derived xenograft mouse models of Pseudomyxoma Peritonei recapitulate the human inflammatory tumor microenvironment. Cancer medicine.

Kurkjian, C., Murgo, A.J. and Kummar, S., 2008. Treatment of recurrent metastatic colon cancer in the age of modern adjuvant therapy. Clinical colorectal cancer, 7(5), pp.321-324.

Laguinge, L., Bajenova, O., Bowden, E., Sayyah, J., Thomas, P. and Juhl, H., 2005. Surface expression and CEA binding of hnRNP M4 protein in HT29 colon cancer cells. Anticancer research, 25(1A), pp.23-31.

Lee, Y.J., Han, S.R., Kim, N.Y., Lee, S.H., Jeong, J.S. and Lee, S.W., 2012. An RNA aptamer that binds carcinoembryonic antigen inhibits hepatic metastasis of colon cancer cells in mice. Gastroenterology, 143(1), pp.155-165.

Leusch, H.G., Drzeniek, Z., Hefta, S.A., Markos-Pusztai, Z. and Wagener, C., 1991. The putative role of members of the CEA-gene family (CEA, NCA and BGP) as ligands for the bacterial colonization of different human epithelial tissues. Zentralblatt für Bakteriologie, 275(1), pp.118-122.

Leusch, H.G., Hefta, S.A., Drzeniek, Z., Hummel, K., Markos-Pusztai, Z. and Wagener, C., 1990. Escherichia coli of human origin binds to carcinoembryonic antigen (CEA) and non-specific crossreacting antigen (NCA). FEBS letters, 261(2), pp.405-409.

Li, Y., Cao, H., Jiao, Z., Pakala, S.B., Sirigiri, D.N.R., Li, W., Kumar, R. and Mishra, L., 2010. Carcinoembryonic antigen interacts with TGF-β receptor and inhibits TGF-β signaling in colorectal cancers. Cancer research, 70(20), pp.8159-8168.

Li, R., Hebert, J.D., Lee, T.A., Xing, H., Boussommier-Calleja, A., Hynes, R.O., Lauffenburger, D.A. and Kamm, R.D., 2016. Macrophage-secreted TNFα and TGFβ1 Influence Migration Speed and Persistence of Cancer Cells in 3D Tissue Culture via Independent Pathways. Cancer Research, pp.canres-0442.

Lohani, K., Shetty, S., Sharma, P., Govindarajan, V., Thomas, P. and Loggie, B., 2014. Pseudomyxoma Peritonei: inflammatory responses in the peritoneal microenvironment. Annals of surgical oncology, 21(5), pp.1441-1447.

Maeda, M., Nagawa, H., Maeda, T., Koike, H. and Kasai, H., 1998. Alcohol consumption enhances liver metastasis in colorectal carcinoma patients. Cancer, 83(8), pp.1483-1488.

Marko, M., Leichter, M., Patrinou-Georgoula, M. and Guialis, A., 2010. hnRNP M interacts with PSF and p54 nrb and co-localizes within defined nuclear structures. Experimental cell research, 316(3), pp.390-400

Martin, O.A., Anderson, R.L., Narayan, K. and MacManus, M.P., 2017. Does the mobilization of circulating tumor cells during cancer therapy cause metastasis?. Nature Reviews Clinical Oncology, 14(1), pp.32-44.

Massagué, J., 2008. TGFβ in cancer. Cell, 134(2), pp.215-230.

McVicker, B., Tuma, D.J., Lazure, K.E., Thomas, P. and Casey, C.A., 2015. Alcohol, carcinoembryonic antigen processing and colorectal liver metastases. In Biological Basis of Alcohol-Induced Cancer (pp. 295-311). Springer International Publishing.

Millikan, K.W., Staren, E.D. and Doolas, A., 1997. Invasive therapy of metastatic colorectal cancer to the liver. Surgical Clinics of North America, 77(1), pp.27-48.

Moertel, C.G., Fleming, T.R., Macdonald, J.S., Haller, D.G., Laurie, J.A., Tangen, C.M., Ungerleider, J.S., Emerson, W.A., Tormey, D.C., Glick, J.H. and Veeder, M.H., 1995. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Annals of internal medicine, 122(5), pp.321-326.

Moertel, C.G., O'Fallon, J.R., Go, V.L., O'Connell, M.J. and Thynne, G.S., 1986. The preoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of colorectal cancer. Cancer, 58(3), pp.603-610.

Mohr, AM. Gould, JJ. Kubik, JL. Talmon, GA. Casey, CA, Thomas, P. Tuma, D.J. McVicker, BL. Enhanced colorectal cancer metastases in the alcohol-injured liver, Clin Exp. Metastasis 2017, (in press)

Morse, M.A., Nair, S.K., Mosca, P.J., Hobeika, A.C., Clay, T.M., Deng, Y., Boczkowski, D., Proia, A., Neidzwiecki, D., Clavien#, P.A. and Hurwitz, H.I., 2003. Immunotherapy with Autologous, Human Dendritic Cells Transfected with Carcinoembryonic Antigen mRNA: . Cancer investigation, 21(3), pp.341-349.

Nelson, D.E., Jarman, D.W., Rehm, J., Greenfield, T.K., Rey, G., Kerr, W.C., Miller, P., Shield, K.D., Ye, Y. and Naimi, T.S., 2013. Alcohol-attributable cancer deaths and years of potential life lost in the United States. American Journal of Public Health, 103(4), pp.641-648.

Nordlinger, B., Guiguet, M., Vaillant, J.C., Balladur, P., Boudjema, K., Bachellier, P. and Jaeck, D., 1996. Surgical resection of colorectal carcinoma metastases to the liver: a prognostic scoring system to improve case selection, based on 1568 patients. Cancer, 77(7), pp.1254-1262.

Orava, E.W., Abdul-Wahid, A., Huang, E.H.B., Mallick, A.I. and Gariépy, J., 2013. Blocking the attachment of cancer cells in vivo with DNA aptamers displaying anti-adhesive properties against the carcinoembryonic antigen. Molecular oncology, 7(4), pp.799-811.

Ordoñez, C., Screaton, R.A., Ilantzis, C. and Stanners, C.P., 2000. Human carcinoembryonic antigen functions as a general inhibitor of anoikis. Cancer Research, 60(13), pp.3419-3424.

Palermo, N.Y., Thomas, P., Murphy, R.F. and Lovas, S., 2012. Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M. Journal of Peptide Science, 18(4), pp.252-260

Paschos, K.A., Majeed, A.W. and Bird, N.C., 2014. Natural history of hepatic metastases from colorectal cancer-pathobiological pathways with clinical significance. World Journal of Gastroenterology: WJG, 20(14), p.3719

Polyak, K. and Weinberg, R.A., 2009. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nature Reviews Cancer, 9(4), pp.265-273.

Prager, G.W., Braemswig, K.H., Martel, A., Unseld, M., Heinze, G., Brodowicz, T., Scheithauer, W., Kornek, G. and Zielinski, C.C., 2014. Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab‐based treatment response in metastatic colorectal cancer. Cancer science, 105(8), pp.996-1001.

Rees, M., Tekkis, P.P., Welsh, F.K., O'rourke, T. and John, T.G., 2008. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Annals of surgery, 247(1), pp.125-135.

Rehm, J. and Shield, K.D., 2014. Alcohol and mortality: global alcohol-attributable deaths from cancer, liver cirrhosis, and injury in 2010. Alcohol research: current reviews, 35(2), p.174.

Rokavec, M., Öner, M.G., Li, H., Jackstadt, R., Jiang, L., Lodygin, D., Kaller, M., Horst, D., Ziegler, P.K., Schwitalla, S. and Slotta-Huspenina, J., 2014. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. The Journal of clinical investigation, 124(4), pp.1853-1867.

Rougier, P., Laplanche, A., Huguier, M., Hay, J.M., Ollivier, J.M., Escat, J., Salmon, R., Julien, M., Roullet Audy, J.C. and Gallot, D., 1992. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. Journal of Clinical Oncology, 10(7), pp.1112-1118.

Ruers, T. and Bleichrodt, R.P., 2002. Treatment of liver metastases, an update on the possibilities and results. European Journal of Cancer, 38(7), pp.1023-1033.
Sack, T.L., Gum, J.R., Low, M.G. and Kim, Y.S., 1988. Release of carcinoembryonic antigen from human colon cancer cells by phosphatidylinositol-specific phospholipase C. Journal of Clinical Investigation, 82(2), p.586.

Samara, R.N., Laguinge, L.M. and Jessup, J.M., 2007. Carcinoembryonic antigen inhibits anoikis in colorectal carcinoma cells by interfering with TRAIL-R2 (DR5) signaling. Cancer research, 67(10), pp.4774-4782.

Shanmugathasan, M. and Jothy, S., 2000. Apoptosis, anoikis and their relevance to the pathobiology of colon cancer. Pathology international, 50(4), pp.273-279.

Siegel, R.L., Miller, K.D. and Jemal, A., 2015. Cancer statistics, 2015. CA: a cancer journal for clinicians, 65(1), pp.5-29.

Soeth, E., Wirth, T., List, H.J., Kumbhani, S., Petersen, A., Neumaier, M., Czubayko, F. and Juhl, H., 2001. Controlled ribozyme targeting demonstrates an anti-apoptotic effect of carcinoembryonic antigen in HT29 colon cancer cells. Clinical cancer research, 7(7), pp.2022-2030.

Stangl, R., Altendorf-Hofmann, A., Charnley, R.M. and Scheele, J., 1994. Factors influencing the natural history of colorectal liver metastases. The Lancet, 343(8910), pp.1405-1410.

Steeg, P.S., 2006. Tumor metastasis: mechanistic insights and clinical challenges. Nature medicine, 12(8), p.895.

Tibbetts, L.M., Doremus, C.M., Tzanakakis, G.N. and Vezeridis, M.P., 1993. Liver metastases with 10 human colon carcinoma cell lines in nude mice and association with carcinoembryonic antigen production. Cancer, 71(2), pp.315-321.

Thomas, P., Forse, R.A. and Bajenova, O., 2011. Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver. Clinical & experimental metastasis, 28(8), pp.923-932.

Thomas, P., Gangopadhyay, A., Steele, G., Andrews, C., Nakazato, H., Oikawa, S. and Jessup, J.M., 1995. The effect of transfection of the CEA gene on the metastatic behavior of the human colorectal cancer cell line MIP-101. Cancer letters, 92(1), pp.59-66.

Thomas P, Kuracha M, Loggie, B and Govindarajan V. Carcinoembryonic Antigen (CEA): A Potential Mediator of Inflammation in Pseudomyxoma Peritonei. 25th Annual International CEA Symposium, Washington DC, August 17th 2015.

Thomas, P., Toth, C.A., Saini, K.S., Jessup, J.M. and Steele, G., 1990. The structure, metabolism and function of the carcinoembryonic antigen gene family. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1032(2-3), pp.177-189.

Thomas, P. and Zamcheck, N., 1983. Role of the liver in clearance and excretion of circulating carcinoembryonic antigen (CEA). Digestive diseases and sciences, 28(3), pp.216-224.

Thomas, P., Zamcheck, N., Rogers, A.E. and Fox, J.G., 1982. Plasma clearance of carcinoembryonic antigen and asialo carcinoembryonic antigen by the liver of the nutritionally deficient rhesus monkey. Clinics in laboratory medicine, 2(3), p.459.

Thompson, J.A., Grunert, F. and Zimmermann, W., 1991. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. Journal of clinical laboratory analysis, 5(5), pp.344-366.

Tobi, M., Kim, M., Zimmer, R., Hatfield, J., Kam, M., Khoury, N., Carville, A., Lawson, M.J., Schiemann, W.P. and Thomas, P., 2011. Colorectal cancer in the cotton top tamarin (Saguinus oedipus): how do they evade liver metastasis?. Digestive diseases and sciences, 56(2), pp.397-405.

Tobi, M., Thomas, P. and Ezekwudo, D., 2016. Avoiding hepatic metastasis naturally: Lessons from the cotton top tamarin (Saguinus oedipus). World Journal of Gastroenterology, 22(24), p.5479.

Toth, C.A., 1992. Carcinoembryonic antigen binding proteins on elicited peritoneal macrophages. Journal of leukocyte biology, 51(5), pp.466-471.

Toth, C.A., Rapoza, A., Zamcheck, N., Steele, G. and Thomas, P., 1989. Receptor-mediated endocytosis of carcinoembryonic antigen by rat alveolar macrophages in vitro. Journal of leukocyte biology, 45(4), pp.370-376.

Toth, C.A., Thomas, P., Broitman, S.A. and Zamcheck, N., 1982. A new Kupffer cell receptor mediating plasma clearance of carcinoembryonic antigen by the rat. Biochemical Journal, 204(2), pp.377-381.

Toth, C.A., Thomas, P., Broitman, S.A. and Zamcheck, N., 1985. Receptor-mediated endocytosis of carcinoembryonic antigen by rat liver Kupffer cells. Cancer research, 45(1), pp.392-397.

Torre, L.A., Bray, F., Siegel, R.L., Ferlay, J., Lortet‐Tieulent, J. and Jemal, A., 2015. Global cancer statistics, 2012. CA: a cancer journal for clinicians, 65(2), pp.87-108.

Vauthey, J.N., Marsh, R.D.W., Cendan, J.C., Chu, N.M. and Copeland, E.M., 1996. Arterial therapy of hepatic colorectal metastases. British journal of surgery, 83(4), pp.447-455.

Ueda, Y., Itoh, T., Nukaya, I., Kawashima, I., Okugawa, K., Yano, Y., Yamamoto, Y., Naitoh, K., Shimizu, K., Imura, K. and Fuji, N., 2004. Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived. HLA-A24-restricted CTL epitope: Clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas. International journal of oncology, 24(4), pp.909-918.


Venook, A.P. and Warren, R.S., 1996. Regional chemotherapy approaches for primary and metastatic liver tumors. Surgical oncology clinics of North America, 5(2), pp.411-427.

Wagner, H.E., Thomas, P., Wolf, B.C., Zamcheck, N., Jessup, J.M. and Steele Jr, G.D., 1989. Characterization of the tumorigenic and metastatic potential of a poorly differentiated human colon cancer cell line. Invasion & metastasis, 10(5), pp.253-266.

Wagner, H.E., Toth, C.A., Steele, G.D. and Thomas, P., 1992. Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production. Clinical & experimental metastasis, 10(1), pp.25-31.

Wang, T., Notta, F., Navab, R., Joseph, J., Ibrahimov, E., Xu, J., Zhu, C.Q., Borgida, A., Gallinger, S. and Tsao, M.S., 2017. Senescent Carcinoma-Associated Fibroblasts Upregulate IL8 to Enhance Prometastatic Phenotypes. Molecular Cancer Research, 15(1), pp.3-14.

Weidle, U.H., Birzele, F. and Krüger, A., 2015. Molecular targets and pathways involved in liver metastasis of colorectal cancer. Clinical & experimental metastasis, 32(6), pp.623-635.

Wirth, T., Soeth, E., Czubayko, F. and Juhl, H., 2002. Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic rate of colon cancer cells and inhibits metastatic tumor growth. Clinical & experimental metastasis, 19(2), pp.155-160.

Yan,, C. Hu, Y. Zhang, B. Mu, L. Huang, K. Zhao, H. Ma, C. Li, X. Tao, D. Gong, J. Qin, J. 2016. The CEA-/I0 colorectal cancer cell population harbors cancer stem cells and metastatic cells. Oncotarget, 7 (49) pp.80700-80715

Zamcheck, N., 1981. The expanding field of colorectal cancer markers: CEA, the prototype. Cancer Bull, 33, pp.141-151.

Zang, M., Zhang, B., Zhang, Y., Li, J., Su, L., Zhu, Z., Gu, Q., Liu, B. and Yan, M., 2014. CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway. PloS one, 9(11), p.e112908.

Zhang, Y., Zang, M., Li, J., Ji, J., Zhang, J., Liu, X., Qu, Y., Su, L., Li, C., Yu, Y. and Zhu, Z., 2014. CEACAM6 promotes tumor migration, invasion, and metastasis in gastric cancer. Acta biochimica et biophysica Sinica, 46(4), pp.283-290.

Zimmer, R. and Thomas, P., 2001. Mutations in the Carcinoembryonic Antigen Gene in Colorectal Cancer Patients. Cancer research, 61(7), pp.2822-2826.

Zhou, H., Fuks, A., Alcaraz, G., Bolling, T.J. and Stanners, C.P., 1993. Homophilic adhesion between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds. The Journal of cell biology, 122(4), pp.951-960.

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