INBIOSUR   25013
INSTITUTO DE CIENCIAS BIOLOGICAS Y BIOMEDICAS DEL SUR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
PTHrP treatment of colon cancer cells enhances angiogenesis through VEGF
Autor/es:
CARRIERE, PEDRO; GENTILI, CLAUDIA; MARTÍN, MA. JULIA; CALVO, NATALIA; NOVOA DIAZ, BELEN
Lugar:
Ciudad Autónoma de Buenos Aires
Reunión:
Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017
Institución organizadora:
Sociedades de Biociencias
Resumen:
Angiogenesis plays a critical role in tumor growth and involves multiple processes including the secretion of angiogenic factors by tumor cell and the increase of endothelial cell mobility and its differentiation. We found that Parathyroid Hormone-related Peptide (PTHrP) induces the proliferation and migration of Caco-2 and HCT116 cells, two cell lines from human colon tumors. Using both cell lines, the objective of this work was to study if the hormone is also implicated in tumor angiogenesis. qPCR assay revealed that mRNA levels of VEGF, HIF-1alpha and MMP-9, which are factors involved in angiogenesis, are increased after PTHrP treatment for 20 h in both cell lines. To test tumor angiogenic potential of PTHrP in vitro we evaluated the migratory properties of the human endothelial cell line HMEC-1 employing transwell inserts and a chemoattractant source, which is conditionedcultured media (CM) from Caco-2 or HCT 116 cells exposed to PTHrP for 24 h. Results showed that CM from cells treated with the hormone markedly increases the migration of endothelial cells. Similar data were obtained using co-culture. In addition, we performed tube formation assays using growth factor-reduced Geltrex. HMEC-1 cells incubated with CM from non-treated Caco-2 or HCT 116 cells formed few tube-like structures on geltrex whereas the CM from colon cancer cells treated with PTHrP increased tube formation of HMEC-1 cells. In contrast, by direct treatment the hormone not stimulated migration neither tube formation of HMEC-1 cells. Finally, studies with neutralizing antibody against VEGF revealed that augmented angiogenic response of endothelial cells exposed to CM from colon cancer cells treated with PTHrP was associated with enhanced production of VEGF. In summary, the results obtained from this study show that PTHrP treatment of colon cancer cells promotes pro-angiogenic signaling.