Tenascin-C and Integrin α9 Mediate Interactions of Prostate Cancer with the Bone Microenvironment

Cancer Res. 2017 Nov 1;77(21):5977-5988. doi: 10.1158/0008-5472.CAN-17-0064. Epub 2017 Sep 15.

Abstract

Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here, we report that tenascin C is expressed in the bone endosteum and is associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin C exhibited enhanced adhesion and colony formation as mediated by integrin α9β1. In addition, metastatic cells preferentially migrated and colonized tenascin-C-coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of fertilized chicken eggs as host. Overall, our studies deepen knowledge about reactive stroma responses in the bone endosteum that accompany prostate cancer metastasis to trabecular bone, with potential implications to therapeutically target this process in patients. Cancer Res; 77(21); 5977-88. ©2017 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Chick Embryo
  • Chorioallantoic Membrane / metabolism
  • Integrins / genetics
  • Integrins / metabolism*
  • Male
  • Organoids / metabolism
  • Organoids / pathology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Binding
  • RNA Interference
  • Tenascin / metabolism*

Substances

  • Integrins
  • Tenascin
  • integrin alpha 9 beta 1