Cells interact with extracellular matrix molecules by specific receptors. We have characterized membrane binding molecules for fibronectin and collagen. The distribution of fibronectin receptors was disrupted to a diffuse pattern after transformation of avian cells. This alteration could be mimicked by treatment of normal cells with a synthetic peptide that blocks receptor function, and it could be partially reverted by treatment of transformed cells with exogenous cellular fibronectin. This receptor was found to be required for a developmentally- regulated invasive event in which hemopoietic precursor cells transiently gain the ability to invade across basement membranes in vivo and in vitro. A related fibronectin receptor equivalent to the human Ic-IIa complex was discovered on platelets, and it was shown to function in platelet adherence to fibronectin. A key role for carbohydrate processing in the acquisition of fibronectin receptor function is being examined. We have also further characterized a major 47K collagen-binding protein that we found to be a transformation-sensitive, novel heat-shock regulated glycoprotein, whose phosphorylation was increased after transformation. Immunofluorescence and immunoelectron microscopic studies localized it primarily to the endoplasmic reticulum; it was expressed in cell-type specific patterns in vivo. Its binding to collagen was regulated by pH, with maximal release of bound ligand at pH 6.3. This finding permitted its isolation in native form and determination of a unique N-terminal 36-amino sequence. We will further characterize this and other collagen- binding proteins, exploring the role of fibronectin and collagen receptors in cell adhesion, migration, and invasion.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB008717-10
Application #
3939321
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code