HMMR maintains the stemness and tumorigenicity of glioblastoma stem-like cells

Cancer Res. 2014 Jun 1;74(11):3168-79. doi: 10.1158/0008-5472.CAN-13-2103. Epub 2014 Apr 7.

Abstract

Glioblastoma (GBM) stem cells (GSC) are a subpopulation of tumor cells that display stem-like characteristics (stemness) and play unique roles in tumor propagation, therapeutic resistance, and tumor recurrence. Therapeutic targets in GSCs are a focus of increasing interest to improve GBM therapy. Here we report that the hyaluronan-mediated motility receptor (HMMR) is highly expressed in GBM tumors, where it supports the self-renewal and tumorigenic potential of GSCs. HMMR silencing impairs GSC self-renewal and inhibits the expression of GSC markers and regulators. Furthermore, HMMR silencing suppresses GSC-derived tumor growth and extends the survival of mice bearing GSC xenografts. Conversely, HMMR overexpression promotes GSC self-renewal and intracranial tumor propagation. In human GBM tumor specimens, HMMR expression is correlated positively with the expression of stemness-associated markers and regulators. Our findings identify HMMR as a candidate therapeutic target to GSCs as a GBM treatment strategy.

Publication types

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

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology*
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology*
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism*
  • Mice
  • Mice, SCID
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*

Substances

  • Extracellular Matrix Proteins
  • Hyaluronan Receptors
  • hyaluronan-mediated motility receptor