Decreased tumorigenicity in vivo when transforming growth factor beta treatment causes cancer cell senescence.
We have previously reported that transforming growth factor beta (TGF-beta) triggers two independent senescence programs, 1) replicative senescence dependent upon telomere shortening and 2) premature senescence independent of telomere shortening, in the cell line of A549 human lung adenocarcinoma. In this study, we examined the possibility that cancer cell tumor phenotypes could be suppressed by forced senescence. We used A549 cells treated with TGF-beta for a long time (over 50 days), where senescence was induced in a telomere-shortening-dependent or an independent way. Fully senescent A549 cells were elongated, acquired contact inhibition capabilities when reaching confluence, and secreted the senescence-associated cytokine IL-6. Furthermore, senescent A549 cells had no tumorigenicity in nude mice. These results indicate that the forced induction of senescence in cancer cells may be a novel and potentially powerful method for advancing anti-cancer therapy.
Katakura
Yoshinori
Y
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan. katakura@grt.kyushu-u.ac.jp
Nakata
Eriko
E
Tabira
Yukiko
Y
Miura
Takumi
T
Teruya
Kiichiro
K
Tsuchiya
Toshie
T
Shirahata
Sanetaka
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D003260:Contact Inhibition / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009374:Neoplasms, Experimental / Q000517:prevention & control; D051785:Smad Proteins; D016615:Telomere / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta