The interaction of the tumor cell with its extracellular matrix may play an important role in determining its metastatic and invasive properties. To better understand the protein components that make up the extracellular matrix, their regulation and how they interact with the tumor cell, we have undertaken to construct, isolate, and characterize molecular clones of laminin receptor and of several different collagens. Laminin receptor is a cell surface protein to which laminin (a major component of basement membrane) specifically binds with high affinity. We previously isolated a human laminin receptor cDNA which encoded the carboxy-terminal half of the protein and showed that laminin receptor mRNA in the tumor cell is a rate-limiting control step in the biosynthesis of the receptor, and hence in the regulation of cellular attachment to basement membranes via laminin. During the past year, we have extended our sequence analysis of the laminin receptor gene. In particular, we have obtained more amino terminal sequences. We have discovered that there is more than one laminin receptor gene which may encode more than one protein expressed in the cell. We have also cloned a murine laminin receptor cDNA and have found that murine cells, like their human counterparts, have multiple laminin receptor genes. Studies of the regulation of the laminin receptor gene indicate that differentiated cells express less laminin receptor mRNA than do related, undifferentiated precursor cells. This is consistent with the general observation that aggressive undifferentiated tumors which metastasize express more laminin receptor.
