In situ analysis of integrin and growth factor receptor signaling pathways in human glioblastomas suggests overlapping relationships with focal adhesion kinase activation

Markus J. Riemenschneider, Wolf Mueller, Rebecca Betensky, Gayatry Mohapatra, David N. Louis

Research output: Contribution to journalArticle

Abstract

Deregulated integrin signaling is common in cancers, including glioblastoma. Integrin binding and growth factor receptor signaling activate focal adhesion kinase (FAK) and subsequently up-regulate extracellular regelated kinases (ERK-1/2), leading to cell-cycle progression and cell migration. Most studies of this pathway have used in vitro systems or tumor lysate-based approaches. We examined these pathways primarily in situ using a panel of 30 glioblastomas and gene expression arrays, immunohistochemistry, and fluorescence in situ hybridization, emphasizing the histological distribution of molecular changes. Within individual tumors, increased expression of FAK, p-FAK, paxillin, ERK-1/2, and p-ERK-1/2 occurred in regions of elevated EGFK and/or PDGFRA expression. Moreover, FAK activation levels correlated with EGFR and PDGFRA expression, and p-FAK and EGFR expression co-localized at the single-cell level. In addition, integrin expression was enriched in EGFR/PDGFRA-overexpressing areas but was more regionally confined than FAK, p-FAK, and paxillin. Integrins β8 and α5β1 were most commonly expressed, often in a perinecrotic or perivascular pattern. Taken together, our data suggest that growth factor receptor overexpression facilitates alterations in the integrin signaling pathway. Thus, FAK may act in gliobiastoma as a downstream target of growth factor signaling, with integrals enhancing the impact of such signaling in the tumor microenvironment.

Original languageEnglish (US)
Pages (from-to)1379-1387
Number of pages9
JournalAmerican Journal of Pathology
Volume167
Issue number5
DOIs
StatePublished - Jan 1 2005

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Focal Adhesion Protein-Tyrosine Kinases
Growth Factor Receptors
Glioblastoma
Integrins
Paxillin
Neoplasms
Tumor Microenvironment
Fluorescence In Situ Hybridization
Cell Movement
Intercellular Signaling Peptides and Proteins
Cell Cycle
Phosphotransferases
Up-Regulation
Immunohistochemistry
Gene Expression

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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In situ analysis of integrin and growth factor receptor signaling pathways in human glioblastomas suggests overlapping relationships with focal adhesion kinase activation. / Riemenschneider, Markus J.; Mueller, Wolf; Betensky, Rebecca; Mohapatra, Gayatry; Louis, David N.

In: American Journal of Pathology, Vol. 167, No. 5, 01.01.2005, p. 1379-1387.

Research output: Contribution to journalArticle

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