Human soluble delta-like 1 homolog exerts antitumor effects in vitro and in vivo

Biochem Biophys Res Commun. 2016 Jun 24;475(2):209-15. doi: 10.1016/j.bbrc.2016.05.076. Epub 2016 May 15.

Abstract

Proteolysis of delta-like 1 homolog (DLK1), a cell-surface transmembrane protein, produces an active soluble form of DLK1 (sDLK1). Both membrane-bound DLK1 and sDLK1 modulate multiple developmental processes including adipogenesis, osteogenesis, chondrogenesis and myogenesis. However, cancer-related functions of DLK1 have not yet been established. We thus evaluated the roles of extracellular sDLK1, comprising six EGF-like domains and juxtamembrane regions, in human pancreatic cancer MIA PaCa-2 cells in vitro and in vivo. We observed that sDLK1 exerted antitumor effects not only in cancer cell migration and anchorage-independent cell growth but also in in vivo tumor growth.

Keywords: Cancer; Delta-like 1 homolog; Extracellular soluble DLK1; Membrane protein; Proteolysis.

MeSH terms

  • Animals
  • BALB 3T3 Cells
  • Calcium-Binding Proteins
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / analysis
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Nude
  • Pancreas / metabolism*
  • Pancreas / pathology*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Protein Domains
  • Proteolysis

Substances

  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins