The laminin receptor and basement membrane dissolution: role in tumour metastasis

Tumour invasion and metastasis is a complex process involving multiple interactions of tumour cells with host cellular and extracellular elements. Metastasizing tumour cells traverse basement membranes at many stages in the metastatic cascade. Immunohistology studies demonstrate that the basement membranes are defective in all human malignant epithelial neoplasms studied to date. The basement membrane is absent in regions of microinvasion and adjacent to actively invading tumour cells. In contrast, benign neoplasms retain a continuous basement membrane. This distinction may have diagnostic value in surgical pathology. Tumour cells are hypothesized to traverse basement membranes by a three-step process: attachment, local degradation of the basement membrane by type IV collagenase and other proteases, and locomotion. The first step may be mediated in part by specific cell surface receptors which bind to laminin in the basement membrane. The laminin receptor has been purified from a series of different human carcinomas. The receptor has an Mr of 67 000 and a binding coefficient of 2 nM. The content of unoccupied receptors is markedly augmented in invasive human breast cancer compared to benign controls.