Defining the role of laminin-332 in carcinoma

Abstract

The deadly feature of cancer, metastasis, requires invasion of cells through basement membranes (BM), which normally act as barriers between tissue compartments. In the case of many epithelially-derived cancers (carcinomas), laminin-332 (Ln-332) is a key component of the BM barrier. This review provides a historical examination of Ln-332 from its discovery through identification of its functions in BM and possible role in carcinomas. Current understanding points to distinct roles for the three Ln-332 subunits (alpha3, beta3, gamma2) in cell adhesion, extracellular matrix stability, and cell signaling processes in cancer. Given the large number of studies linking Ln-332 gamma2 subunit with cancer prognosis, particular attention is given to the crucial role of this subunit in cancer invasion and to the unanswered questions in this area.

Fig. 1

Laminin-332 structure and major roles. Representation of Ln-332 heterotrimer is shown. The long arm of the molecule contains all chains held in a coiled structure by disulfide linkage. The G domain, consisting of 5 LG modules (red circles beneath the long arm), of the α chain is responsible for various cellular functions. LG modules 1–3 are important for integrin binding important for cell signaling. LG modules 3 and 4 are important for proteolytic processing, and modules LG4 and LG5 interact and bind with heparin and proteoglycans (reviewed in Marinkovich, 2007). The β and γ short arms contain cleavable interaction domains with crucial ECM interaction and growth factor-like signaling functions.