ORIGINAL RESEARCH article
Front. Med.
Sec. Pathology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1652589
Proangiogenic effects of peritumoral adipose tissue in kidney cancer
Provisionally accepted
Matías Ferrando
Nadia Bannoud
Fiorella Campo-Verde-ArboccoLeonardo Rafael RomeoMatilde Constanza López-Fontana
Rubén Walter Carón
Flavia BrunaDiego Omar Croci
Virginia Pistone-Creydt*- CONICET Mendoza, Mendoza, Argentina
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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. Results: 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.
Keywords: Human adipose tissue, renal cancer, Angiogenesis, Epithelial-stromal interactions, Endothelial cells migration
Received: 23 Jun 2025; Accepted: 22 Aug 2025.
Copyright: © 2025 Ferrando, Bannoud, Campo-Verde-Arbocco, Romeo, López-Fontana, Carón, Bruna, Croci and Pistone-Creydt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Virginia Pistone-Creydt, CONICET Mendoza, Mendoza, Argentina
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