Expression of human choriogonadotropin-like material correlates with metastatic phenotype of R3230 AC rat adenocarcinoma.
Human choriogonadotropin (hCG)-like material has been found in variable amounts on the surface of cells of human and animal tumors. Intravenous injection of R3230 AC rat adenocarcinoma cells, one of the models investigated, results in multiple lung foci seeding. We analyzed the phenotypic diversity of this tumor by cloning and culturing two distinct cell subpopulations from a cell culture of this tumor, hereafter called OR or original cell culture. One was obtained after repeated exposure of the OR to increasing concentrations of concanavalin A and wheat germ agglutinin. A single clone was isolated and was named lectin-resistant (LR) cell line. The LR cells did not metastasize but maintained stable tumorigenicity and morphology over at least 10 passages. A second cell line was obtained by repeated passage and injection of cells from a single metastatic node. After repeating the process five times, a single clone of cells was selected from the final variant and was called lung metastatic (LM) cell line. The LM cultured cells maintained stable tumorigenicity, morphology, and metastatic properties for no more than 10 passages. OR, LR, and LM cells were assessed by their doubling time (DT), chromosome counts, and hCG immunocytochemistry. The results demonstrated that the LM cell line had a higher chromosome count than the LR and the OR cell lines, and its DT was the shortest. Immunocytochemistry of the transplanted OR neoplasm showed scattered expression of the hCG-like material. By the same techniques a complete lack of reactivity of the LR cells was found. However, almost all cells of the LM line were strongly positive for hCG-like material. After a few passages, the great majority of the LM cells also became unreactive. Our data demonstrate: (i) the existence of marked heterogeneity of the expression of hCG-like material in the primary tumor cell population; (ii) that the expression of hCG-like material correlates with the metastasizing capacity of the cells; and (iii) that there is a phenotypic instability for the expression of hCG-like material by tumor cells when maintained in vitro.
D000230:Adenocarcinoma / Q000032:analysis* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000032:analysis*; D008325:Mammary Neoplasms, Experimental / Q000032:analysis* / Q000473:pathology; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010641:Phenotype; D051381:Rats; D014407:Tumor Cells, Cultured / Q000032:analysis* / Q000637:transplantation
D006063:Chorionic Gonadotropin