Accession Number : ADA338862

Title :   Novel Tissue Inhibitor of Metalloproteinase, TIMP-4, in Human Breast Cancer Growth and Metastasis

Descriptive Note : Annual rept. 1 Oct 96-30 Sep 97

Corporate Author : LONG ISLAND JEWISH-HILLSIDE MEDICAL CENTER NEW HYDE PARK NY

Personal Author(s) : Shi, Yuenian E.

PDF Url : ADA338862

Report Date : OCT 1997

Pagination or Media Count : 31

Abstract : We recently identified, cloned, and characterized a novel human tissue inhibitor of metalloproteinases-4, TIMP-4. To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, we transfected a full-length TIMP-4 cDNA into MDA-MB-43 5 human breast cancer cells and studied the orthotopic growth of TIMP-4-transfected (TIMP4-435) versus control (neo-435) clones in the mammary fat pad of athymic nude mice. Overexpression of TIMP-4 inhibited the invasion potential of the cells in the in vitro invasion assay. When injected orthotopically into nude mice, TIMP-4 transfectants were significantly inhibited in tumor growth by 4-10-fold in primary tumor volumes; and in an axillary lymph node and lung metastasis as compared with controls. Purified recombinant TIMP4 protein demonstrated a strong inhibitory effect on the invasion of human breast cancer cells across reconstituted basement membranes. These results suggest the therapeutic potential of TIMP-4 in treating cancer malignant progression.

Descriptors :   *TISSUES(BIOLOGY), *PEPTIDE HYDROLASES, *METASTASIS, *BREAST CANCER, HUMANS, ENZYMES, NEOPLASMS, IN VITRO ANALYSIS, LUNG, MEMBRANES, CLONES, MICE, INHIBITORS, CELLS(BIOLOGY), AMINO ACIDS, GROWTH(PHYSIOLOGY), LYMPH NODES.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE