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Tumor microenvironment tenascin-C promotes glioblastoma invasion and negatively regulates tumor proliferation.

Publication ,  Journal Article
Xia, S; Lal, B; Tung, B; Wang, S; Goodwin, CR; Laterra, J
Published in: Neuro Oncol
April 2016

BACKGROUND: Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor in adults. Recent research on cancer stroma indicates that the brain microenvironment plays a substantial role in tumor malignancy and treatment responses to current antitumor therapy. In this work, we have investigated the effect of alterations in brain tumor extracellular matrix tenascin-C (TNC) on brain tumor growth patterns including proliferation and invasion. METHODS: Since intracranial xenografts from patient-derived GBM neurospheres form highly invasive tumors that recapitulate the invasive features demonstrated in human patients diagnosed with GBM, we studied TNC gain-of-function and loss-of function in these GBM neurospheres in vitro and in vivo. RESULTS: TNC loss-of-function promoted GBM neurosphere cell adhesion and actin cytoskeleton organization. Yet, TNC loss-of-function or exogenous TNC had no effect on GBM neurosphere cell growth in vitro. In animal models, decreased TNC in the tumor microenvironment was accompanied by decreased tumor invasion and increased tumor proliferation, suggesting that TNC regulates the "go-or-grow" phenotypic switch of glioma in vivo. We demonstrated that decreased TNC in the tumor microenvironment modulated behaviors of stromal cells including endothelial cells and microglia, resulting in enlarged tumor blood vessels and activated microglia in tumors. We further demonstrated that tumor cells with decreased TNC expression are sensitive to anti-proliferative treatment in vitro. CONCLUSION: Our findings suggest that detailed understanding of how TNC in the tumor microenvironment influences tumor behavior and the interactions between tumor cells and surrounding nontumor cells will benefit novel combinatory antitumor strategies to treat malignant brain tumors.

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Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

April 2016

Volume

18

Issue

4

Start / End Page

507 / 517

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Microenvironment
  • Tumor Cells, Cultured
  • Tenascin
  • Rats, Inbred Lew
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Neoplasm Invasiveness
  • Mice, SCID
  • Mice
 

Citation

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Xia, S., Lal, B., Tung, B., Wang, S., Goodwin, C. R., & Laterra, J. (2016). Tumor microenvironment tenascin-C promotes glioblastoma invasion and negatively regulates tumor proliferation. Neuro Oncol, 18(4), 507–517. https://doi.org/10.1093/neuonc/nov171
Xia, Shuli, Bachchu Lal, Brian Tung, Shervin Wang, C Rory Goodwin, and John Laterra. “Tumor microenvironment tenascin-C promotes glioblastoma invasion and negatively regulates tumor proliferation.Neuro Oncol 18, no. 4 (April 2016): 507–17. https://doi.org/10.1093/neuonc/nov171.
Xia S, Lal B, Tung B, Wang S, Goodwin CR, Laterra J. Tumor microenvironment tenascin-C promotes glioblastoma invasion and negatively regulates tumor proliferation. Neuro Oncol. 2016 Apr;18(4):507–17.
Xia, Shuli, et al. “Tumor microenvironment tenascin-C promotes glioblastoma invasion and negatively regulates tumor proliferation.Neuro Oncol, vol. 18, no. 4, Apr. 2016, pp. 507–17. Pubmed, doi:10.1093/neuonc/nov171.
Xia S, Lal B, Tung B, Wang S, Goodwin CR, Laterra J. Tumor microenvironment tenascin-C promotes glioblastoma invasion and negatively regulates tumor proliferation. Neuro Oncol. 2016 Apr;18(4):507–517.
Journal cover image

Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

April 2016

Volume

18

Issue

4

Start / End Page

507 / 517

Location

England

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Tumor Microenvironment
  • Tumor Cells, Cultured
  • Tenascin
  • Rats, Inbred Lew
  • Oncology & Carcinogenesis
  • Neoplastic Stem Cells
  • Neoplasm Invasiveness
  • Mice, SCID
  • Mice