Laminin Isoforms in Tumor Invasion, Angiogenesis and Metastasis

Laminins are a growing family of alphabetagamma heterotrimeric proteins, commonly found in basement membranes (BMs). These large molecules promote cell adhesion and migration via integrins and other cell-surface receptors. Over 12 laminin isoforms are presently known. The various isoforms have a cell- and tissue-specific expression and are differentially recognized by integrins. Expression of laminin isoforms in tumors usually reflects expression in their normal counterparts. However, during tumor invasion, loss of the BM barrier occurs and a discontinuous pattern of laminin staining is observed. In carcinomas, tumor cells at the invading front strongly express intracellularly the gamma2 chain, a component of laminin-5. Remodeling of the vascular BM is observed during angiogenesis, and penetration of several BMs occurs during tumor dissemination and metastasis. Thus, disregulated cell-laminin interactions are major traits of malignant disorders.