Role of SPARC in the epithelial-mesenchymal transition induced by PTHrP in human colon cancer cells

CARRIERE P; LOPEZ-MONCADA F; ALONSO E; CONTRERAS HR; CALVO N (COMPARTE PRIMERA AUTORÍA); HERRERA A; GANDINI NA; GENTILI C; NOVOA DÍAZ MB; TORRES MJ; GIGOLA G

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Año: 2021 vol. 530 p. 1 - 13

0303-7207

Parathyroid hormone-related peptide (PTHrP) exerts its effects on cells derived from colorectal cancer (CRC) and tumor microenvironment and is involved in processes requiring the epithelial-mesenchymal transition (EMT). Here, we report that PTHrP modulates factors expression and morphological changes associated with EMT in HCT116 cells from CRC. PTHrP increased the protein expression of SPARC, a factor involved in EMT, in HCT116 cells but not in Caco-2 cells also from CRC but with less aggressiveness. PTHrP also increased SPARC expression and its subsequent release from endothelial HMEC-1 cells. The conditioned media of PTHrP-treated HMEC-1 cells induced early changes related to EMT in HCT116 cells. Moreover, SPARC treatment on HCT116 cells potentiated PTHrP modulation in E-cadherin expression and cell migration. In vivo PTHrP also increased SPARC expression and decreased E-cadherin expression. These results suggest a novel PTHrP action on CRC progression involving the microenvironment in the modulation of events associated with EMT.