Human
androgen-dependent
prostate cancer LNCaP cells are low tumorigenic even in immunodeficient mice and were killed by the synergistic effect of inflammatory
cytokines, IL-beta and
IL-6. To establish a highly tumorigenic LNCaP cell line, we isolated the
cytokine-resistant LNCaP-CR cell line and examined the phenotypes. The parental LNCaP cells were induced to commit apoptosis by the addition of IL-1beta and
IL-6, but LNCaP-CR cells showed strong resistance against the
cytokine action. However, LNCaP-CR cells did not exhibit any resistance to various
antitumor drugs investigated. While LNCaP cells formed only palpable
tumors in SCID mice, LNCaP-CR cells readily made
tumors and their growth was significantly higher than that of LNCaP cells. Moreover, LNCaP
tumor-bearing mice gained the weight gradually, but LNCaP-CR
tumor-bearing mice significantly lost their
body weight. LNCaP-CR cells still responded to
androgen action and expressed AR, erbB2, IL-1R, IL-6R, gp130, STAT3, p21, Bcl-2 and
caspase-3 as well as LNCaP cells. These results indicate that LNCaP-CR cell line is a new type of tumorigenic LNCaP cell lines and should be useful for identifying responsible genes of tumorigenicity,
cytokine resistance, and also
cachexia.