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-β and IL-6. To establish a highly tumorigenic LNCaP cell line, we isolated the cytokine-resistant LNCaP-CR cell line and exami...

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Bibliographic Details
Published in:Cancer letters 2006-10, Vol.242 (1), p.46-52
Main Authors: Kawada, Manabu, Inoue, Hiroyuki, Usami, Ihomi, Takamoto, Kozo, Masuda, Tohru, Yamazaki, Yoko, Ikeda, Daishiro
Format: Article
Language:English
Subjects:
Animals
Cell growth
Cell Line, Tumor
Cytokines
Cytokines - metabolism
Deoxyribonucleic acid
DNA
DNA Fragmentation
Drug Resistance, Neoplasm
Experiments
Gene expression
Gene Expression Regulation, Neoplastic
Genetic testing
Humans
Inflammation
Inflammatory cytokine
Interleukin-1beta - metabolism
Interleukin-6 - metabolism
LNCaP
Male
Mice
Mice, SCID
Phenotype
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
Proteins
Statistical analysis
Tumorigenicity
Tumors
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Summary: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-β 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-1β 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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2005.10.040