Abstract
The relationship between cellular differentiation and carcinoembryonic antigen (CEA) production by human colorectal tumor cells and their ability to form hepatic metastases was studied. Eight human colon cancer cell lines were injected into athymic mice using different routes of administration to characterize their metastatic potential. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver after intrasplenic injection. After intraperitoneal implantation the same cell lines were highly tumorigenic, and subsequently metastastic to the liver. In contrast, the four moderate to well-differentiated cell lines that produced moderate to high levels of CEA were highly metastatic to the liver following intrasplenic injection. After intraperitoneal implantation they were less tumorigenic, and metastatic to the liver. We conclude that in this system poorly differentiated non or low CEA producing colorectal cell lines have a lower metastatic capacity compared to the well-differentiated high CEA producing colorectal cell lines. These data correlate directly with the pattern of metastatic spread and clinical course observed in patients with these tumors, suggesting that degree of differentiation and level of CEA production may play a role in development of site-specific metastases.
Similar content being viewed by others
References
Silverberg E and Lubera J, 1987, Cancer Statistics. CA. 37, 2–19.
Saenz NC, Cady B, McDermott WV and Steele GD Jr, 1989, Experience with colorectal carcinoma metastatic to the liver. Surg. Clin. North America, 69, 361–370.
Olson RM, Perencevich NP, Malcolm AW, Chaffey JT and Wilson RE, 1980, Patterns of recurrence following curative resection of adenocarcinoma of the colon and rectum. Cancer, 45, 2969–2974.
Steinberg SM, Barwick KW and Stablein DM, 1986, Importance of tumor pathology and morphology in patients with surgically resected colon cancer. Cancer, 58, 1340–1345.
Daneker G, Piazza A, Steele G and Mercurio A, 1989, Relationship between extracellular matrix interactions and degree of differentiation in human colon carcinoma cell lines. Cancer Research, 49, 681–686.
Wagner H, Thomas P, Wolf B, Zamcheck N, Jessup J and Steele G, 1990, Characterization of the tumorigenic and metastatic potential of a poorly differentiated human colorectal cancer cell line. Invasion and Metastasis, 10, 253–266.
Willet C, Tepper J and Cohen A, 1984, Failure patterns following curative resection of colonic carcinoma. Annals of Surgery, 200, 685–692.
Boucher D, Cournoyer D, Stanners C and Fuks A, 1989, Studies on the control of gene expression of carcinoembryonic antigen family in human tissue. Cancer Research, 49, 847–852.
Benchimol S, Fuks A, Jothy S, Beauchemin N, Shirota K and Stanners C, 1989, Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell, 57, 327–334.
Turbide C, Rojas M, Stanners C and Beauchemin N, 1991, A mouse carcinoembryonic antigen gene family member is a calcium dependent cell adhesion molecule. Journal of Biological Chemistry, 266, 309–315.
Jessup JM, Giavazzi R, Campbell D, Cleary K, Morikawa K and Fidler I, 1988, Growth potential of human colorectal carcinomas in nude mice: association with the preoperative serum concentration of carcinoembryonic antigen in patients. Cancer Research, 48, 1689–1692.
Goslin R, Steele G Jr, MacIntyre J, Mayer R, Sugarbaker P, Cleghorn K, Wilson R, and Zamcheck N, 1980, The use of preoperative plasma CEA levels for the stratification of patients after curative resection of colorectal cancers. Annals of Surgery, 192, 747–751.
Steele G Jr and Zamcheck N, 1985, The use of carcinoembryonic antigen in the clinical management of patients with colorectal cancer. Cancer Detection and Prevention, 8, 421–427.
Thomas P and Zamcheck N, 1983, Role of liver in clearance and excretion of circulating carcinoembryonic antigen (CEA). Digestive Diseases and Sciences, 28, 216–224.
Niles R, Wilhelm S, Steele G, Burke B, Christensen T, Dexter D, O'Brien M, Thomas P and Zamcheck N, 1987, Isolation and characterization of an un differentiated human colon carcinomas cell line (MIP101). Cancer Investigations, 5, 545–552.
Koslowski J, Fidler I, Campbell D, Xu Z, Kaighn M and Hart I, 1984, Metastatic behaviour of human tumor cell lines grown in the nude mouse. Cancer Research, 44, 3522–3529.
Morrisey L, Sidky Y and Auerbach R, 1980, Regional differences in the growth of tumor cells injected intraperitoneally into syngeneic adult mice. Cancer Research, 40, 2197–2201.
Daneker G, Mercurio A, Guerra L, Wolf B, Salem R, Bagh D and Steele G, 1987, Laminin expression in colorectal carcinomas varying in degree of differentiation. Archives of Surgery, 122, 1470–1474.
Bennet D, Dexter T, Ormerod E and Hart I, 1986, Increased metastatic capacity of a murine melanoma following induction of differentiation. Cancer Research, 46, 3239–3244.
Toth CA, 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, 370–376.
Gjoren T, Seljelid R and Kolset S, 1989, Binding of metastatic colon carcinoma cells to liver macrophages. Journal of Leukocyte Biology, 45, 370–376.
Keller F, Wild M and Krin A, 1989, In vitro properties of unactivated rat Kupffer cells. Journal of Leukocyte Biology, 35, 467–474.
Hostetter RB, Augustus IB, Mankarious R, Chi KF, Fan D, Toth C, Thomas P and Jessup JM, 1990, Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. Journal of the National Cancer Institute, 82, 380–385.
Liotta L, Kleinerman J and Saidel G, 1976, The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Research, 36, 889–894.
Jessup J and Thomas P, 1989, Carcinoembryonic antigen: function in metastases by human colorectal carcinoma. Cancer Metastases Review, 8, 263–280.
Thomas P and Toth CA, 1989, Site of carcinoembryonic antigen binding to Kupffer cells. Biochemical Society Transactions, 17, 1121–1122.
O'Brien M, Bronstein B, Zamcheck N, Saravis C, Burke B and Gottlieb LS, 1980, Cholestasis and hepatic metastases: a factor contributing to extreme elevations of carcinoembryonic antigen. Journal of the National Cancer Institute, 64, 1291–1294.
Weiss L, Grundmann E, Torhorst J, Hartveit F, Moberg I, Eder M, Fenoglio-Preiser C, Napier J, Horne C, Lopez M, Shaw-Dunn R, Sugar J, Davies J, Day D and Harlos J, 1986, Hematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. Journal of Pathology, 150, 195–203.
Kyriazis A, DiPersio L, Michael G, Pesce A and Stinnett J, 1978, Growth patterns and metastatic behaviour of human tumors growing in athymic mice. Cancer Research, 38, 3186–3190.
Giavazzi R, Jessup J, Campbell D, Walker S and Fidler I, 1986, Experimental nude mouse model of human colorectal cancer liver metastases. Journal of the National Cancer Institute, 77, 1303–1308.
Bresalier R, Hujanen E, Raper S, Roll J, Itzkowwitz S, Martin G and Kim Y, 1987, An animal model for colon cancer metastasis: establishment and charcterization of murine cell lines with enhanced liver metastasizing ability. Cancer Research, 47, 1398–1406.
Giavazzi R, Campbell D, Jessup J, Cleary K and Fidler I, 1986, Metastatic behaviour of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice. Cancer Research, 46, 1928–1933.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wagner, H.E., Toth, C.A., Steele, G.D. et al. Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production. Clin Exp Metast 10, 25–31 (1992). https://doi.org/10.1007/BF00163573
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00163573