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IFN‐gamma specifically targets melanoma stem cells and inhibits in vitro spherogenic growth
Author(s) -
Lee ChungWei,
Huang John,
Chuang YaTing,
Murphy George F
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1087.11
Subject(s) - melanoma , cancer research , immune system , biology , immunology , stem cell , cancer cell , cancer stem cell , cell growth , cancer immunotherapy , cancer , immunotherapy , microbiology and biotechnology , genetics
The host immune system can suppress development and progression of cancer. Recent success in cancer immunotherapy validates anti‐cancer strategies by activating innate and adaptive immune responses or suppressing regulatory and inhibitory mechanisms. Among immune modulators, interferon gamma (IFNg) is of special interest because it affects both host immunity and cancer cell kinetics. IFNg has antiproliferative and proapoptotic effects in cancer cells. However, recent data has challenged this paradigm in melanoma cells, suggesting that macrophage‐derived IFNg actually may promote growth of mouse melanomas in vivo . To examine the effect of IFNg in human melanoma cells, we observed that IFNg suppressed growth of susceptible melanoma cell lines A2058 and A375 in a STAT1‐dependent manner, and decreased anchorage‐independent spherogenic growth, an in vitro correlate of cancer stem cell tumorigenicity in animal xenotransplantation models. Interestingly, IFNg did not alter melanoma cell cycle progression or induce apoptosis at the minimal dose that is sufficient to suppress spherogenic growth. IFNg was shown to downregulate mRNA expression of the melanoma stem cell‐associated transcription factor OCT4, and upregulate the tumor suppressor gene XAF1. In conclusion, IFNg specifically suppresses in vitro spherogenic growth that characterizes melanoma stem cells. (NIH NCI R01 CA138231 and T32 HL007627)