Accession Number : ADA303464

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

Descriptive Note : Annual rept. 30 Sep 94-29 Sep 95,

Corporate Author : VIRGINIA UNIV CHARLOTTESVILLE

Personal Author(s) : Gonias, Steven L.

PDF Url : ADA303464

Report Date : OCT 1995

Pagination or Media Count : 22

Abstract : For breast cancer cells to invade or metastasize, a cascade of proteinases, including the serine proteinase plasmin, must be organized at the cell surface. In the first year of this research program, we demonstrated a unique mechanism whereby breast cancer cells bind plasmin. The putative receptor S cytokeratin 8 (CK 8). CK 8 is a cytoskeletal protein; however, using fluorescence microscopy and unoelectron microscopy, we demonstrated CK 8 on the external plasma membrane of non-permeablized breast cancer cells. We prepared a monoclonal antibody specific for a synthetic peptide corresponding to the C-terminal 13 amino acids of CK 8. This antibody bound specifically to breast cancer cells and inhibited binding of plasminogen to the same cells. Furthermore, we demonstrate that purified CK 8 not only binds plasminogen, but also tissue-type plasminogen activator. In the resulting ternary complex, the rate of plasminogen activation is significantly increased. This activity is duplicated by CK 8 which is recovered from conditioned medium of breast cancer cell lines. We are now developing the reagents to test the role of CK 8 in breast cancer invasion, using in vitro invasion models.

Descriptors :   *MAMMARY GLANDS, *PLASMIN, *METASTASIS, *BREAST CANCER, TEST AND EVALUATION, ACTIVATION, FLUORESCENCE, PEPTIDES, PLASMAS(PHYSICS), RATES, IN VITRO ANALYSIS, MICROSCOPY, SURFACES, CHEMICAL AGENTS, MEMBRANES, ANTIBODIES, EXTERNAL, MONOCLONAL ANTIBODIES, CELLS(BIOLOGY), ENZYME PRECURSORS, PEPTIDE HYDROLASES, SERINE.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE