Establishment of a highly tumorigenic LNCaP cell line having inflammatory cytokine resistance.
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.
Kawada
Manabu
M
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
Inoue
Hiroyuki
H
Usami
Ihomi
I
Takamoto
Kozo
K
Masuda
Tohru
T
Yamazaki
Yoko
Y
Ikeda
Daishiro
D
D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D053938:DNA Fragmentation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6