Invasion-Associated Reorganization of Laminin 332 in Oral Squamous Cell Carcinomas: The Role of the Laminin γ2 Chain in Tumor Biology, Diagnosis, and Therapy

SIMPLE SUMMARY: The destructive growth of carcinomas is associated with crossing the border between the epithelial and the connective tissue parts of an organ. One component of this borderline, the basement membrane, is the heterotrimeric laminin 332, which mediates the adhesion of basal epithelial cells. This protein, in particular its gamma 2 chain, is fundamentally reorganized during tumor cell invasion. Specific deposition patterns of laminin 332 are also present in oral squamous cell carcinomas and have been shown to be of high diagnostic and predictive value. Furthermore, laminin 332 restructuring is associated with important tumor biological processes, e.g., stromal activation, the development of a motile phenotype, and tumor spreading. In this review, current knowledge in the field is summarized and the recommendation to consider laminin 332 as a promising grading and monitoring parameter and as a potential therapeutic target is discussed. ABSTRACT: Invasion of the connective tissue by carcinoma cells is accompanied by disintegration and reorganization of the hemidesmosomes, which connect the basement membrane to the basal epithelial cells. In terms of mediating the basement membrane, i.e., basal cell interactions, the heterotrimeric laminin 332 is the most important bridging molecule. Due to this distinct function, laminin 332, especially its gamma 2 chain, came into the focus of cancer research. Specific de novo synthesis and deposition patterns of laminin 332 are evident upon development and progression of oral squamous cell carcinomas (OSCCs). Loss from the basement membrane, cytoplasmic accumulation, and extracellular deposition are associated with crucial processes such as stromal activation and immune response, epithelial to mesenchymal transition, and tumor cell budding. In networks with components of the tumor microenvironment, altered expression of laminin 332 chains, proteolytic processing, and interaction with integrin receptors seem to promote cancer cell migration. Indeed, reorganization patterns are shown to have a high diagnostic and prognostic value. Here, we summarize the current knowledge on laminin 332 reorganization in OSCCs with special focus on its gamma 2 chain and provide, based on the current literature, evidence on its promising role as a grading and monitoring parameter and as a potential therapeutic target.