An understanding of cell-substratum adhesion and interaction at the cellular and molecular level provides useful information concerning cell proliferation and differentiation and the relevance of these processes to malignancy. Mammalian cells in culture are capable of responding to a number of extracellular matrix proteins as mediators of attachment and spreading. Our laboratory is studying serum spreading factor (SF), an attachment-promoting glycoprotein present both in blood and extracellular matrix and synthesized by human hepatoma cells in vitro. SF appears to be the presursor for Somatomedin B, a growth hormone-responsive peptide present in plasma, urine and amniotic fluid, and recently also has been found to be identical to S Protein, an inhibitor of complement-mediated cell lysis and thrombin inactivation. In this proposal we describe continuations of our work toward the definition of relationships between the structure and the biological actions of this molecule. We will study the molecular specificities and significance of SF with components of extracellular matrix. For this work we will examine proteolytic fragments and synthetic peptides derived from distinct domains of the molecule for the ability to mimic or to function as competitive inhibitors of SF action. We also propose to identify the cell types involved is SF synthesis in adult organisms and to begin determining the mechanisms of regulation of SF expression in liver cells. For this work we will quantitate SF messenger RNA and protein synthesis and employ hepatoma and primary liver cell cultures. We hope that an understanding of the mechanism by which SF influences cell adhesion and the physiological influences affecting SF synthesis and deposition will contribute to a molecular explanation of normal and aberrant cell-substratum interactions, neoplasia and metastasis.
