Open AccessEndogenous tenascin‐C enhances glioblastoma invasion with reactive change of surrounding brain tissue
Author(s) -
Hirata Eishu,
Arakawa Yoshiki,
Shirahata Mitsuaki,
Yamaguchi Makoto,
Kishi Yo,
Okada Takashi,
Takahashi Jun A.,
Matsuda Michiyuki,
Hashimoto Nobuo
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01189.x
Subject(s) - tenascin c , tenascin , extracellular matrix , cancer research , gene knockdown , focal adhesion , tyrosine kinase , biology , integrin , pathology , microbiology and biotechnology , signal transduction , medicine , cell , cell culture , fibronectin , genetics
Tenascin‐C is an extracellular matrix glycoprotein implicated in embryogenesis, wound healing and tumor progression. We previously revealed that tenascin‐C expression is correlated with the prognosis of patients with glioblastoma. However, the exact role of endogenous tenascin‐C in regulation of glioblastoma proliferation and invasion remains to be established. We show here that endogenous tenascin‐C facilitates glioblastoma invasion, followed by reactive change of the surrounding brain tissue. Although shRNA‐mediated knockdown of endogenous tenascin‐C does not affect proliferation of glioblastoma cells, it abolishes cell migration on a two‐dimensional substrate and tumor invasion with brain tissue changes in a xenograft model. The tyrosine phosphorylation of focal adhesion kinase, a cytoplasmic tyrosine kinase that associates with integrins, was decreased in tenascin‐C‐knockdown cells. In the analysis of clinical samples, tenascin‐C expression correlates with the volume of peritumoral reactive change detected by magnetic resonance imaging. Interestingly, glioblastoma cells with high tenascin‐C expression infiltrate brain tissue in an autocrine manner. Our results suggest that endogenous tenascin‐C contributes the invasive nature of glioblastoma and the compositional change of brain tissue, which renders tenascin‐C as a prime candidate for anti‐invasion therapy for glioblastoma. ( Cancer Sci 2009)