Establishment of a highly tumorigenic LNCaP cell line having inflammatory cytokine resistance |
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Authors: | Kawada Manabu Inoue Hiroyuki Usami Ihomi Takamoto Kozo Masuda Tohru Yamazaki Yoko Ikeda Daishiro |
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Institution: | Drug Development Unit, Numazu Bio-Medical Research Institute, Microbial Chemistry Research Center, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan. kawadam@bikaken.or.jp |
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Abstract: | 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. |
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