Elevated expression of TGF-β1 in head and neck cancer-associated fibroblasts

Eben Rosenthal, Allison McCrory, Melissa Talbert, Geoff Young, Joanne Murphy-Ullrich, Candece Gladson

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Head and neck cancers are characterized by a vigorous desmoplastic response, but the contribution of stromal-derived growth factors to the tumor microenvironment is poorly understood. We evaluated the expression of stromal growth factor expression in head and neck squamous cell carcinoma (HNSCC) in normal and tumor-associated stromal cells. Stromal tissue was isolated from epithelial cells with laser capture microdissection (LCMD) and analyzed by cDNA array for the expression of TGFα, TGF-β1, HGF, PDGF-α, IGFII, bFGF, aFGF, VEGFC, and VEGF. Primary fibroblasts were isolated in vitro from HNSCC tumors, adjacent histologically normal mucosa, and skin in vitro. Fibroblast populations were assessed for TGF-β1 expression by ELISA and luciferase reporter assay to assess protein expression. We identified TGF-β1 and IGFII overexpression in normal and tumor-associated stromal cells; however, only TGF-β1 was significantly overexpressed (3.4-fold) in tumor-associated stroma. Assessment of carcinoma-associated fibroblasts (CAFs), normal dermal fibroblasts (NDFs), and normal mucosal fibroblasts (NMFs) in propagated fibroblasts demonstrated persistently elevated levels of TGF-β1 in CAFs compared to NMF and NDF populations. Elevated levels of TGF-β1 were identified in the stromal compartment of HNSCC tumors compared to normal mucosa by immunohistochemical analysis. These results suggest that TGF-β1 mRNA and protein is specifically upregulated in CAFs in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)116-121
Number of pages6
JournalMolecular Carcinogenesis
Volume40
Issue number2
DOIs
StatePublished - Jun 1 2004

Keywords

  • Carcinoma-associated fibroblasts
  • Head and neck cancer
  • Squamous-cell carcinoma
  • Stroma
  • TGF-β1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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  • Cite this

    Rosenthal, E., McCrory, A., Talbert, M., Young, G., Murphy-Ullrich, J., & Gladson, C. (2004). Elevated expression of TGF-β1 in head and neck cancer-associated fibroblasts. Molecular Carcinogenesis, 40(2), 116-121. https://doi.org/10.1002/mc.20024