Open AccessHypoxia and low‐nutrition double stress induces aggressiveness in a murine model of melanoma
Author(s) -
Osawa Tsuyoshi,
Muramatsu Masashi,
Watanabe Makoto,
Shibuya Masabumi
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01105.x
Subject(s) - hypoxia (environmental) , melanoma , carcinogenesis , cancer research , regulator , cancer cell , biology , protein kinase b , in vivo , cancer , population , medicine , endocrinology , microbiology and biotechnology , chemistry , signal transduction , gene , genetics , environmental health , organic chemistry , oxygen
Antiangiogenic therapy is a potent cancer treatment, however, the possibility of recurrence and resistance to this approach remains. Here we show that hypoxia and low‐nutrition double‐deprivation stress induces reversible tumor aggressiveness. In a stress‐cycle‐dependent manner, murine melanoma cells showed morphological changes, up‐regulated phospho‐Akt, and abnormal regulation of multiple genes including fibroblast growth factor‐21, a metabolic regulator, resulting in increased cell proliferation in vitro , and increased tumorigenesis and invasive potential in vivo . In this system, altered cellular metabolism participates in the adaptation of tumor to the double‐deprivation stress. Our results suggest the targeting of a minor population of cancer cells resistant to both hypoxia and low nutrition to be an effective new antitumor strategy in combination with antiangiogenic therapy. ( Cancer Sci 2009; 100: 844–851)