Human renal adipose tissue induces the invasion and progression of renal cell carcinoma

Abstract

// Fiorella Campo-Verde-Arbocco 1 , José D. López-Laur 2, 7 , Leonardo R. Romeo 3 , Noelia Giorlando 1 , Flavia A. Bruna 1 , David E. Contador 6 , Gastón López-Fontana 2 , Flavia E. Santiano 1 , Corina V. Sasso 1 , Leila E. Zyla 1 , Constanza M. López-Fontana 1 , Juan C. Calvo 4, 5 , Rubén W. Carón 1 and Virginia Pistone Creydt 1, 7 1 Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Centro Científico y Tecnológico Mendoza, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mendoza, Argentina 2 Clinica Andina de Urología, Mendoza, Argentina 3 Departamento de Urología y Transplante Renal, Hospital Español, Mendoza, Argentina 4 Instituto de Biología y Medicina Experimental (IBYME), Buenos Aires, Argentina 5 Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina 6 Centro de Medicina Regenerativa, Facultad de Medicina, Clinica Alemana, Universidad del Desarrollo, Santiago, Chile 7 Universidad Nacional de Cuyo, Facultad de Ciencias Médicas, Mendoza, Argentina Correspondence to: Virginia Pistone Creydt, email: vpistone@mendoza-conicet.gob.ar Keywords: human adipose tissue, renal epithelial cells, cancer, epithelial-stromal interactions, migration Received: December 08, 2016     Accepted: August 29, 2017     Published: October 09, 2017 ABSTRACT We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease.