The hypoxia that arises due to the rapid proliferation of tumor cells is a fundamental driving force for the canonical pathway of neovascularization. In the current study we report a very strong correlation between mRNA expression levels of HIF-2α (but not HIF-1α), VEGFR-1, VEGFR-2 and MMP2 in ex vivo samples from laryngeal carcinoma. Sixty-three samples from patients with histopathologically verified carcinoma of the larynx were examined in this study. Total RNA was isolated from both normal and tumor fresh frozen tissues of each patient and real-time quantitative PCR reactions were performed. The mRNA expression levels of HIF-1α, HIF-2α, VEGFR1, VEGFR2 and MMP2 were acquired. We found strong positive correlations between mRNA expression levels of HIF-2α and VEGFR-1, r s (98) = .671, p < .0005; HIF-2α and VEGFR-2, r s (98) = .742, p < .0005; HIF-2α and MMP2, r s (98) = .566, p < .0005; VEGFR-1 and VEGFR-2, r s (98) = .791, p < .0005; VEGFR-1 and MMP2, r s (98) = .709, p < .0005; VEGFR-2 and MMP2, r s (98) = .793, p < .0005. Our results provide evidence for the regulatory connection between HIF-2α and VEGFR-1, VEGFR-2 and MMP2 in the light of ETS1/ HIF-2α regulatory axis on a non-in-vitro level in carcinoma tissue, uncover some of the differences between the homologues HIF-1α and HIF-2α and round up and support the results from different experimental models in this field.
Keywords: Flk-1; Flt-1; HIF-1α; HIF-2α; Laryngeal carcinoma; MMP2; VEGFR1; VEGFR2.