Association between Tumorigenic Potential and the Fate of Cancer Cells in a Syngeneic Melanoma ModelReportar como inadecuado

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The self-renewal potential of a cancer cell can be estimated by using particular assays, which include xenotransplantation in immunocompromised animals or culturing in non-adherent serum-free stem-cells media SCM. However, whether cells with self-renewal potential actually contribute to disease is unknown. Here we investigated the tumorigenic potential and fate of cancer cells in an in-vivo melanoma model. We examined cell lines which were derived from the same parental line: a non-metastatic cell line K1735-16, a metastatic cell line K1735-M4 and a cell line which was selected in non-adherent conditions K1735-16S. All cell lines exhibited similar proliferation kinetics when grown on culture plates. K1735-16 cells grown in soft agar or in suspension non-adherent conditions failed to form colonies or spheroids, whereas the other cell lines showed prominent colonogenicity and spheroid formation capacity. By using sphere limiting dilution analysis SLDA in serum-free media, K1735-16S and K1735-M4 cells grown in suspension were capable of forming spheroids even in low frequencies of concentrations, as opposed to K1735-16 cells. The tumorigenic potential of the cell lines was determined in SCID mice using intra footpad injections. Palpable tumors were evident in all mice. In agreement with the in-vitro studies, the K1735-M4 cell line exhibited the highest growth kinetics, followed by the K1735-16S cell line, whereas the K1735-16 cell line had the lowest tumor growth potential P<0.001. In contrast, when we repeated the experiments in syngeneic C3H-HeN mice, the K1735-16 cell line produced macroscopic tumors 30–100 days after injection, whereas K1735-M4 and K1735-16S derived tumors regressed spontaneously in 90–100% of mice. TUNEL analysis revealed significantly higher number of apoptotic cells in K1735-16S and K1735-M4 cell line-derived tumors compared to K1735-16 tumors P<0.001. The models we have examined here raised the possibility, that cells with high-tumorigenic activity may be more immunogenic and hence are more susceptible to immune-regulation.

Autor: Yakov Krelin , Liron Berkovich, Moran Amit, Ziv Gil



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