Compositions and methods for inhibiting intercellular interactions
Disclosed are compositions and methods involving the use of PRG4 protein, also known as lubricin, to mechanically inhibit biological processes involving cell motility and adhesion. The methods and compositions may be used to develop a variety of specific therapies and compositions, often exploited through surgical procedures, where development of the pathology involves one or more of the following modes of action: 1) the passage of cells from one body compartment to another, 2) adherence of macrophages to substrates such as fibrin or exposed extra cellular matrix, 3) binding of platelets to fibrin, or 4) failure of function of the glycocalyx on exposed epithelial cell surfaces, e.g., within the vasculature. In these instances PRG4 glycoprotein adheres to extracellular matrix or cell surfaces and presents a glycol-surface of polysaccharide which blocks the mechanisms of cell motility, extravasation, or intravasation, inhibits sticking of macrophages and platelets, and/or serves as a substitute or mimic of native glycocalyx.
1. A method of inhibiting in a mammal transient binding interactions between a motile cell and a tissue, the method comprising the step of applying PRG4 to a surface of the motile cell or of the tissue in an amount sufficient to provide a coating which inhibits transient attractive interactions between the cell and the tissue so as to inhibit motility of the cell through, within, or across the surface of the tissue, wherein the motile cell is a neoplastic cell.
2. The method of claim 1 wherein the neoplastic cell is a non-malignant neoplastic cell or a cancer cell.
3. The method of claim 1 , where the PRG4 is applied to the surface of the motile cell or of the tissue by local injection.
4. The method of claim 1 , wherein the PRG4 is applied to provide a dose of between 0.3 mg/kg and 3.0 mg/kg of PRG4 to said mammal.
5. The method of claim 1 , wherein the neoplastic cell is a cancer cell.
6. The method of claim 1 , wherein the PRG4 has the amino acid sequence of residues 25-1404 of SEQ ID NO: 1.
7. The method of claim 2 , wherein the PRG4 has the amino acid sequence of residues 25-1404 of SEQ ID NO:1.
8. The method of claim 3 , wherein the PRG4 has the amino acid sequence of residues 25-1404 of SEQ ID NO:1.
9. The method of claim 4 , wherein the PRG4 has the amino acid sequence of residues 25-1404 of SEQ ID NO:1.
10. The method of claim 5 , wherein the PRG4 has the amino acid sequence of residues 25-1404 of SEQ ID NO:1.