Regulation of HGF and SDF-1 expression by oral fibroblasts – Implications for invasion of oral cancer

• Published in: Oral oncology Vol. 44; no. 7; pp. 646 - 651
• Main Authors: Daly, Aisling J, McIlreavey, Leanne, Irwin, Chris R
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2008; Elsevier
• Subjects: Animals; Biological and medical sciences; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Chemokine CXCL12 - metabolism; Fibroblasts - metabolism; Gene Expression Regulation; Hematology, Oncology and Palliative Medicine; Hepatocyte growth factor; Hepatocyte Growth Factor - metabolism; Humans; Interleukin-1alpha - metabolism; Invasion; Medical sciences; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Myofibroblast; Neoplasm Invasiveness; Neoplasm Proteins - metabolism; Oral squamous cell carcinoma; Otolaryngology; Otorhinolaryngology. Stomatology; Peptide Fragments - metabolism; Stromal cell-derived factor-1; Stromal Cells - pathology; Transforming Growth Factor beta1 - metabolism; Tumors; Tumour–stroma interactions; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Stromal cell-derived factor-1; Tumour–stroma interactions; Oral squamous cell carcinoma; Hepatocyte growth factor; Myofibroblast; Invasion; Oral cancer; Stomatology; Oral administration; Stroma; Tumorous infiltration; ENT; Malignant tumor; Tumour-stroma interactions; Stromal cell derived factor 1; Regulation(control); Cancerology; Oral cavity disease; CXC chemokine; Fibroblast; Cancer
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2007.08.012

Summary Invasion and metastasis of oral squamous cell carcinoma (OSCC) is dependent on signals received from stromal fibroblasts present in the surrounding connective tissue. The aim of this study was to investigate the regulation of expression of two important signaling molecules – HGF and SDF-1 – by both stromal fibroblasts and their ‘activated’ form, myofibroblasts, and to determine the role of these two factors in stimulating OSCC cell invasion in vitro. Fibroblasts and myofibroblasts produced similar levels of HGF and SDF-1. IL-1α and OSCC cell conditioned medium both stimulated HGF and SDF-1 expression, while TGF-β1 inhibited production of each factor. Myofibroblast-derived conditioned medium stimulated OSCC cell invasion through matrigel. Blocking antibodies to both HGF and SDF-1 reduced the level of invasion. In fibroblast-free organotypic raft cultures, addition of HGF and SDF-1 stimulated OSCC cell invasion into the underlying collagen gel, although the pattern of invasion differed from that induced by fibroblasts. Fibroblast-derived HGF and SDF-1 appear to play central roles in the reciprocal interactions between OSCC cells and underlying stromal fibroblasts leading to the local invasion of oral cancer.