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

Mol Cell Endocrinol. 2021 Jun 15:530:111253. doi: 10.1016/j.mce.2021.111253. Epub 2021 Mar 26.

Abstract

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.

Keywords: Colon cancer; EMT; PTHrP; SPARC; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Caco-2 Cells
  • Cadherins / metabolism*
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Culture Media, Conditioned / chemistry
  • Disease Progression
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Mice
  • Neoplasm Transplantation
  • Osteonectin / genetics
  • Osteonectin / metabolism*
  • Parathyroid Hormone-Related Protein / genetics
  • Parathyroid Hormone-Related Protein / metabolism*
  • Tumor Microenvironment
  • Up-Regulation*

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Culture Media, Conditioned
  • Osteonectin
  • PTHLH protein, human
  • Parathyroid Hormone-Related Protein
  • SPARC protein, human