Hypoxia confers resistance to chemoradiation
therapy and promotes
metastasis in
head and neck squamous cell carcinomas (
HNSCC). We investigated the effects of
hypoxia in
tumor phenotype using immunocompetent murine
HNSCC models. Balb/c mice were injected intraorally with murine
squamous cell carcinoma cells LY-2 and B4B8. Intratumoral
hypoxia fraction was evaluated by the immunohistochemical detection of hypoxic probe
pimonidazole and
carbonic anhydrase IX (CAIX).
Tumor cell apoptosis and autophagy in hypoxic areas of these
tumors were examined immunohistochemically.
Hypoxia-induced apoptotic and autophagic responses in vitro were examined by treating LY2 cells with
CoCl(2). B4B8
tumors exhibited a non-aggressive phenotype characterized by its slow growth rate and the lack of metastatic spread. LY2
tumors demonstrated an aggressive phenotype characterized by rapid growth rate with regional and distant
metastasis. Intratumoral
hypoxia fraction in B4B8
tumors was significantly lower than in LY2
tumors. The hypoxic areas in B4B8
tumors exhibited increased apoptosis rate than that of LY2
tumors. In contrast, the hypoxic areas in LY2
tumors revealed autophagy. The induction of
hypoxia in vitro elicited autophagy and not apoptosis in LY2 cells. The induction of autophagy coupled with blockage of apoptosis in hypoxic areas promotes
tumor cell survival and confers aggressive phenotype in immunocompetent murine
HNSCC models.