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.