Endogenous tenascin-C enhances glioblastoma invasion with reactive change of surrounding brain tissue.
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.
Hirata
Eishu
E
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
Arakawa
Yoshiki
Y
Shirahata
Mitsuaki
M
Yamaguchi
Makoto
M
Kishi
Yo
Y
Okada
Takashi
T
Takahashi
Jun A
JA
Matsuda
Michiyuki
M
Hashimoto
Nobuo
N
D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005446:Fluocinolone Acetonide / Q000378:metabolism; D005822:Genetic Vectors; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011859:Radiography; D019063:Tenascin / Q000378:metabolism*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D019063:Tenascin; C485184:enhanced green fluorescent protein; D005446:Fluocinolone Acetonide; D049452:Green Fluorescent Proteins