Proangiogenic effects of peritumoral adipose tissue in kidney cancer

Tumor growth and metastasis require the interaction of tumor cells with the stromal environment. Angiogenesis is a necessary process for tumor growth and metastasis. Previously we showed that the conditioned media (CMs) of human renal adipose tissue from patients with renal tumors (hRAT) increases the migration of tumor and non-tumor renal epithelial cells compared to CMs of normal adipose tissue (hRAN).

We evaluated: (1) mRNA expression of hypoxia inducible factor (HIF) 1α, HIF2α, and vascular endothelial growth factor (VEGF) in hRAN and hRAT, by qRT-PCR; (2) protein expression VEGF in hRAN-CMs and hRAT-CMs, by ELISA; (3) migration of endothelial cells (ECs) incubated with hRAN-CMs and hRAT-CMs, by wound healing assay and transwells; and (4) tube formation by ECs, incubated with hRAN- and hRAT-CMs.

We found a higher expression of HIF1α, HIF2α in hRAT vs. hRAN explants (p < 0.05). Also, we observed a close to significance trend toward higher VEGF protein expression (p = 0.052) in hRAT-CMs vs. hRAN-CMs explants. In addition, we found that hRAT-CMs significantly induced the migration of ECs compared to hRAN-CMs (p < 0.05). Finally, an increased tubulogenesis of ECs incubated with hRAT-CMs vs. hRAN-CMs was observed (p < 0.05).

We show that renal peritumoral adipose tissue secretes VEGF and promotes angiogenesis on HUVEC cell lines, suggesting that VEGF, among other factors, may contribute to this effect. This proangiogenic stimulus would promote the vascularization of the tumor, favoring its growth and metastasis.