Accession Number : ADA323209

Title :   Plasmin-Cellular Interaction in Breast Cancer Invasion and Metastasis.

Descriptive Note : Annual rept. 30 Sep 95-29 Sep 96,

Corporate Author : VIRGINIA UNIV CHARLOTTESVILLE

Personal Author(s) : Gonias, Steven L.

PDF Url : ADA323209

Report Date : OCT 1996

Pagination or Media Count : 39

Abstract : Invasion and metastasis of breast cancer cells requires the function of a cell-surface proteinase cascade in which the proteinase, plasmin, plays a prominent role. Studies of a variety of cell types have shown that the tumor invasion proteinase cascade functions optimally only when plasmin is bound to the cell surface. Different macromolecules may be responsible for plasmin-binding in different cell types. The goal of this research program has been to identify macromolecules responsible for cell-surface immobilization of plasmin in breast cancer cells. In the second year of this research program, we have made significant progress and completed studies identifying cytokeratin-8 as the major plasminogen receptor in three different breast cancer cell lines. Furthermore, we have demonstrated the ability of cytokeratin-8, which is secreted by breast cancer cells, to promote the activation of proteinases involved in tumor invasion in the pericellular spaces. These studies have been published in major journals. We are now exploring the role of cell-surface cytokeratin-8 in breast cancer cell adhesion, migration, and invasion. We have prepared a mutated form of the cytokeratin-8 cDNA for transfection (transfer of function) experiments. Finally, we have initiated studies on plasminogen activator binding to breast cancer cells.

Descriptors :   *CELLS(BIOLOGY), *PLASMIN, *METASTASIS, *BREAST CANCER, TRANSFER FUNCTIONS, ADHESION, NEOPLASMS, MACROMOLECULES, SENSE ORGANS, ENZYME PRECURSORS, PEPTIDE HYDROLASES.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE