Expression of laminin 5-γ2 chain in cutaneous squamous cell carcinoma and its role in tumour invasion

BACKGROUND: Laminin-5 (Ln5), a heterotrimer composed of three chains (alpha 3, beta 3, and gamma 2), is a major component of the basement membrane in most adult tissues. One of the chains, Ln5-gamma 2, is a marker of invasive tumours because it is frequently expressed as a monomer in malignant tumours. Recent studies from our laboratories detected higher levels of Ln5-gamma 2 expression in basal cell carcinoma (BCC) than in trichoblastoma. Furthermore, Ln5-gamma 2 overexpression tended to correlate with aggressiveness in BCC. METHODS: In this study, we compared the expression of Ln5-gamma 2 in invasive squamous cell carcinoma (SCC, n = 62) of the skin to that in preinvasive Bowen's disease (BD, n = 51), followed by analysis of the role of Ln5-gamma 2 in cancer invasion in vitro. RESULTS: Immunohistochemically, the proportion of SCC cases (86%) strongly positive for Ln5-gamma 2 expression was higher than that of BD (16%). Real-time RT-PCR showed Ln5-gamma 2 overexpression in SCC cell line, A431, compared with normal keratinocyte cell line, HaCaT. Ln5-gamma 2 monomer and proteolytically cleaved, biologically active fragments of Ln5-gamma 2 were identified in SCC tumour extracts. In in vitro raft cultures, which simulate in vivo conditions, Ln5-gamma 2 siRNA significantly suppressed epidermal growth factor (EGF)-stimulated A431 cell invasion. CONCLUSION: Our results indicate that Ln5-gamma 2 has a role in cutaneous SCC invasion. British Journal of Cancer (2011) 105, 824-832. doi: 10.1038/bjc.2011.283 www.bjcancer.com Published online 9 August 2011 (C) 2011 Cancer Research UK