PTHrP regulates factors involved in the pathogenesis of colorectal cancer

NOVOA DÍAZ MARÍA BELEN; CALVO NATALIA; GENTILI CLAUDIA; MARTIN MARIA JULIA; CARRIERE, PEDRO; CONTRERAS HECTOR; RIQUELME ALEXANDER

Puerto Varas

Congreso; XXXI Annual Meeting of Chilean Society for Cell Biology.; 2017

Sociedad Chilena de Biología Celular

Introduction: Parathyroid hormone-related peptide (PTHrP) is implicated in several human cancers such as colorectal cancer (CRC). The pathogenesis of this disease involves several processes, including enhanced cell survival, proliferation, migration, invasion, epithelial to mesenchymal transition (EMT) and angiogenesis, as well as anti-tumoral therapy resistance. We found that PTHrP induces the proliferation, cell cycle progression, survival and migration of Caco-2 and HCT116 cells, two cell lines from human colon tumors. Therefore, we propose that PTHrP also modulates the levels of molecular markers associated with other events of CRC progression such as angiogenesis, invasion and EMT. Materials and Methods: We assessed the mRNA levels of MMP-7, VEGF, HIF-1α and MMP-9 by RT-qPCR, protein levels of SPARC and CK-18 by Western-blot and immunocytochemistry in colon cancer cells, treated with or without PTHrP. Results: We observed that PTHrP treatment increases mRNA levels of MMP-7 and the protein expression of SPARC in CRC cells, which are strongly involved in tumor invasion. PTHrP also reduced the protein expression of CK-18, a change associated with EMT and increases mRNA levels of VEGF, HIF-1α and MMP-9, which are factors involved in angiogenesis.Discussion: Our results suggest that PTHrP triggers signaling pathways involved in events that promote the aggressive behavior of intestinal tumor cells, such as angiogenesis, invasion and EMT.