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EGF Receptor Ligands Differentially Promote the Migration and Invasion of Malignant Peripheral Nerve Sheath Tumor Cells
Author(s) -
Byer Stephanie,
Eckert Jenell M,
Watkins Stacey M,
Carroll Steven L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.740.13
Subject(s) - amphiregulin , epiregulin , cancer research , epidermal growth factor , fibronectin , biology , cell migration , heparin binding egf like growth factor , receptor , microbiology and biotechnology , extracellular matrix , cell culture , genetics , biochemistry
Aggressive invasion of adjacent tissues is characteristic of malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy occurring in neurofibromatosis type 1 (NF1). These neoplasms often aberrantly express epidermal growth factor receptors (EGFRs), leading us to hypothesize that EGFR ligands present in MPNSTs and/or adjacent tissues promote MPNST invasion. We have found that EGF promotes MPNST migration in a substrate‐specific manner, enhancing migration on laminin and collagen type I relative to fibronectin. Induction of EGFR shRNA expression in MPNST cells stably transfected with a tetracycline‐regulatable lentivirus reduces baseline migration 40‐60%. Comparing the effects of the known EGFR ligands [EGF, betacellulin, epiregulin, heparin‐binding EGF (HB‐EGF), TGFα, amphiregulin] on MPNST cell lines derived from NF1‐associated (ST88‐14) or sporadic (STS‐26T) neoplasms, we found that these ligands promote migration in a concentration‐dependent manner, with EGF acting in a chemotactic fashion. However, these factors differ in their relative ability to induce migration. Further, although ST88‐14 cells are responsive to all 6 ligands, the STS‐26T migration is not enhanced by HB‐EGF or amphiregulin. These findings suggest that although EGFR ligands enhance MPNST migration and invasion, MPNST responses to these growth factors vary. Supported by grants CA122804 and NS048353.