J C Kim1, S A Roh, K C Park. 1. Department of Surgery, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Seoul, Korea.
Abstract
PURPOSE: Both experimental and clinical results reveal that carcinoembryonic antigen (CEA) seems to mediate some important role in the liver metastasis of colorectal carcinoma cells. The intent of this study was to verify whether adhesive function of CEA might affect liver metastasis in the CEA-expressing colon carcinoma cell line, KM-12c. METHODS: The hepatic binding of [125I]iododeoxyuridine KM-12c cells was measured with or without intravenous CEA pretreatment in four nude mice each. Then, 2 x 10(6) cells of KM-12c were injected into the splenic subcapsule of 57 CEA-pretreated nude mice. KM-12c cells were prepared in phosphate-buffered saline (control, 27 mice) or anti-CEA monoclonal antibody, T84.66 (30 mice). All mice were killed at the end of the eighth week after implant, and tumor nodules were confirmed histologically. RESULTS: Marginal differences of hepatic sequestration were found between the CEA-pretreated mice and the control group. Splenic tumor occurred in 75 percent (18/24) of the control group and in 40 percent (10/25) of the T84.66-pretreated group (P = 0.0107). Forty-two percent (10/24) incurred liver metastasis in the control group, whereas 20 percent (5/25) did so in the T84.66-pretreated group. The number of splenic tumor cells was significantly related to the number and volume of liver metastasis (P = 0.0065). CONCLUSIONS: CEA enhanced liver metastasis predominantly by successful primary tumor implant, whereas primary hepatic entrapment also supported it to some extent in a weakly metastatic colon carcinoma cell line, KM-12c. Tumor cell aggregates seem to be mediated by homophilic binding of CEA molecules, and it is an important mechanism to yield liver metastasis.
PURPOSE: Both experimental and clinical results reveal that carcinoembryonic antigen (CEA) seems to mediate some important role in the liver metastasis of colorectal carcinoma cells. The intent of this study was to verify whether adhesive function of CEA might affect liver metastasis in the CEA-expressing colon carcinoma cell line, KM-12c. METHODS: The hepatic binding of [125I]iododeoxyuridine KM-12c cells was measured with or without intravenous CEA pretreatment in four nude mice each. Then, 2 x 10(6) cells of KM-12c were injected into the splenic subcapsule of 57 CEA-pretreated nude mice. KM-12c cells were prepared in phosphate-buffered saline (control, 27 mice) or anti-CEA monoclonal antibody, T84.66 (30 mice). All mice were killed at the end of the eighth week after implant, and tumor nodules were confirmed histologically. RESULTS: Marginal differences of hepatic sequestration were found between the CEA-pretreated mice and the control group. Splenic tumor occurred in 75 percent (18/24) of the control group and in 40 percent (10/25) of the T84.66-pretreated group (P = 0.0107). Forty-two percent (10/24) incurred liver metastasis in the control group, whereas 20 percent (5/25) did so in the T84.66-pretreated group. The number of splenic tumor cells was significantly related to the number and volume of liver metastasis (P = 0.0065). CONCLUSIONS:CEA enhanced liver metastasis predominantly by successful primary tumor implant, whereas primary hepatic entrapment also supported it to some extent in a weakly metastatic colon carcinoma cell line, KM-12c. Tumor cell aggregates seem to be mediated by homophilic binding of CEA molecules, and it is an important mechanism to yield liver metastasis.
Authors: George S Abi Saad; Maher Hussein; Nagi S El-Saghir; Salah Termos; Ala I Sharara; Ali Shamseddine Journal: Int J Clin Oncol Date: 2011-01-22 Impact factor: 3.402