Suppression of metastases of small cell lung cancer cells in mice by a peptidic CXCR4 inhibitor TF14016

FEBS Lett. 2012 Oct 19;586(20):3639-44. doi: 10.1016/j.febslet.2012.08.011. Epub 2012 Aug 28.

Abstract

CXCL12 is a chemokine essential for the organ-specific spread of a variety of cancers including small cell lung cancer (SCLC). Here, we examined the anti-metastatic efficacy of TF14016, a small peptidic inhibitor of CXCL12 receptor CXCR4, in SCLC. Treatment of mice with TF14016 significantly suppressed pulmonary metastases of CXCR4-expressing SCLC in size and number. Furthermore, histological examination revealed that the expression of vascular endothelial cell growth factor and the density of CD31-positive microvessels in metastatic foci were both significantly reduced in TF14016-treated mice. Collectively, CXCR4 could be an attractive target for anti-metastatic and anti-angiogenic therapy in SCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Chemokine CXCL12 / metabolism
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • Neoplasm Metastasis
  • Peptides / pharmacology*
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Small Cell Lung Carcinoma / metabolism
  • Small Cell Lung Carcinoma / pathology*
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • 4-fluorobenzoyl-Arg-Arg-Nal-Cys-Tyr-Cit-Lys-Lys-Pro-Tyr-Arg-Cit-Cys-Arg-NH2 (S-S bridged)
  • Antineoplastic Agents
  • Chemokine CXCL12
  • Peptides
  • Receptors, CXCR4
  • Vascular Endothelial Growth Factor A