Possible Role and Therapeutic Target of PDGF-D Signalling in Colorectal Cancer

Cancer Invest. 2019;37(2):99-112. doi: 10.1080/07357907.2019.1576191. Epub 2019 Mar 5.

Abstract

Platelet-derived growth factor D (PDGF-D) has been shown to mediate cellular processes of importance in cancer progression. This study aimed to investigate the expression and putative involvement of PDGF-D signaling in colorectal carcinogenesis. PDGF-D was expressed in vascular endothelial cells in tumor and normal tissues. PDGF-D stimulation of cells altered genes of importance in carcinogenic processes. In addition, PDGF-D increased the proliferation rate while imatinib inhibited these effects. PDGF-D and its PDGF receptor beta (PDGFR-β) are expressed in colorectal cancer and blockage of PDGF-D/PDGFR-β signaling using tyrosine kinase inhibitors, such as imatinib, might be important in inhibiting tumor-promoting actions.

Keywords: Angiogenesis; Colorectal cancer; Imatinib; PDGF-D; Proliferation.

MeSH terms

  • Caco-2 Cells
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • HT29 Cells
  • Humans
  • Imatinib Mesylate / pharmacology
  • Lymphokines / metabolism*
  • Platelet-Derived Growth Factor / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Lymphokines
  • PDGFD protein, human
  • Platelet-Derived Growth Factor
  • Protein Kinase Inhibitors
  • Imatinib Mesylate