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

Abstract

Background:Laminin-5 (Ln5), a heterotrimer composed of three chains (α3, β3, and γ2), is a major component of the basement membrane in most adult tissues. One of the chains, Ln5-γ2, 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-γ2 expression in basal cell carcinoma (BCC) than in trichoblastoma. Furthermore, Ln5-γ2 overexpression tended to correlate with aggressiveness in BCC.Methods:In this study, we compared the expression of Ln5-γ2 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-γ2 in cancer invasion in vitro.Results:Immunohistochemically, the proportion of SCC cases (86%) strongly positive for Ln5-γ2 expression was higher than that of BD (16%). Real-time RT–PCR showed Ln5-γ2 overexpression in SCC cell line, A431, compared with normal keratinocyte cell line, HaCaT. Ln5-γ2 monomer and proteolytically cleaved, biologically active fragments of Ln5-γ2 were identified in SCC tumour extracts. In in vitro raft cultures, which simulate in vivo conditions, Ln5-γ2 siRNA significantly suppressed epidermal growth factor (EGF)-stimulated A431 cell invasion.Conclusion:Our results indicate that Ln5-γ2 has a role in cutaneous SCC invasion.

Combinations of laminin 5 with PTEN, p-EGFR and p-Akt define a group of distinct molecular subsets indicative of poor prognosis in patients with non-small cell lung cancer

“…It has been reported that gefitinib inhibits the growth of hepatocellular carcinoma cells, Ln5 reduces the ability of gefitinib to inhibit cell growth and the addition of exogenous Ln5 has no effect on p-EGFR but restores p-Akt (16). Another in vitro study performed using A431 cutaneous squamous cell carcinoma cells reported that Ln5-γ2 siRNA significantly suppressed EGF-stimulated A431 cell invasion (17). In addition, the introduction of Ln5 may activate a survival signal through EGF-independent EGFR activity in certain types of human lung adenocarcinoma cell lines (18).…”

LAMC2 as a therapeutic target for cancers

“…In addition, inhibition of LAMC2 showed reduced cell migration, invasion, wound healing and cell cycle arrest (G1/S phases of cell cycle) of ATC cells [13]. Interestingly, LAMC2 knockdown significantly suppressed the EGF-induced invasion of epidermoid carcinoma cells (A431 cells) [24]. Moreover, cetuximab (EGFR blocking antibody) or EGFR small interfering RNA additively enhanced the antiproliferative effect of LAMC2 knockdown compared to control cells.…”

Invadopodia and basement membrane invasion in vivo

“…It has been known for sometime that cancer cells secrete normal as well as novel basement membrane proteins and matrix-modifying enzymes. [109][110][111][112][113] How this may specifically contribute to invasion and tumor metastasis is poorly understood. Just prior to invasion, the AC secretes the conserved extracellular matrix protein hemicentin specifically under the AC in the basement membrane that will be crossed.…”