Laminin-5 in epithelial tumour invasion.
Laminin-5 (LN-5), consisting of alpha3-, beta3-, and gamma2-chains, is a component of the cell adhesion complex containing hemidesmosomes and anchoring fibrils. This protein is a major constituent of the extracellular matrix and has recently proved to be an invasion marker for epithelial cells in many immunohistochemical surveys, indicating that it is frequently expressed in the invading edges of epithelial tumour cells. Additionally, intracellular accumulation of monomeric gamma2-chains has been widely observed in the invasive carcinoma cells, but its mechanism was not entirely understood. Epithelial carcinoma cells prefer to adhere onto the LN-5-rich basement membranes using the specific integrins as receptors. Induction of cell migration is an important function of LN-5 and the enhanced activity is observed in its truncated form after proteolytic shedding of the N-terminal fragments of gamma2-chains. This processing was demonstrated to be mediated mainly by several kinds of matrix metalloproteinases. The degraded fragments of gamma2-chains, released from invading carcinomas, can be immunodetected in biological fluids and potentially utilized in the clinical diagnosis of various epithelial cancers. Here, we summarize the previous clinical investigations of LN-5 in epithelial tumour progression, and also discuss what it can regulate in the cell physiological events.
Katayama
Masahiko
M
Diagnostic Department, Tsukuba Research Laboratories, Eisai Co., Ltd, Tsukuba, Ibaraki 300-2635, Japan.
Sekiguchi
Kiyotoshi
K
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000503:physiopathology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000097794:Kalinin
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000097794:Kalinin