Absence of Laminin Deposition in Breast Cancer and Metastases except to the Brain

Laminin, a major glycoprotein of basement membrane has been found to play significant roles during invasion and metastases. In this study, we have examined the distribution of laminin in several human brain carcinoma metastases, human breast cancers, skin and lymph node metastases of breast cancer as well as in an in vitro and an in vivo model of invasion. A laminin accumulation was demonstrated a) at the border between human metastatic carcinoma cells and surrounding neural tissue; b) at the invasive edge between MO4 cells (a highly malignant cell line which synthesizes large amounts of laminin) and host tissues of syngenic mice; c) at the front of invasion between MO4 cells and precultured heart fragments in an in vitro model of invasion. Laminin, but not type IV collagen, promoted attachment of MO4 cells. This attachment was inhibited by preincubation of laminin matrix support with (+)-catechin, a flavonoid which also prevented invasion of the precultured heart fragment in vitro. Our data demonstrate that laminin accumulates between malignant cells and host tissue in human brain metastases and in an in vitro and an in vivo model of invasion. In these later models, accumulation of laminin is the consequence, at least in part, of its biosynthesis by MO4 cells. Since laminin promotes attachment of malignant cells in vitro, increases invasiveness and metastatic activities of murine malignant cells, it is tempting to speculate that laminin synthesized by invasive cells and accumulated at the front of invasion plays a significant role in the first step of invasion.