Accession Number : ADA332609

Title :   Nitric Oxide in Mammary Tumor Progression.

Descriptive Note : Annual rept.,


Personal Author(s) : Lala, Peeyush K.

PDF Url : ADA332609

Report Date : JUL 1997

Pagination or Media Count : 149

Abstract : Nitric Oxide (NO) is a potent bioactive product of many normal cells and certain cancer cells. Recently we have shown that tumor-derived NO promoted tumor growth and metastasis in the C3H/HeJ mouse mammary adenocarcinoma model, and that NO induced by IL-2 therapy was responsible for capillary leakage and compromised antitumor effects of IL-2 therapy. Current proposal was to validate further the stimulatory role of NO in tumor progression, and identify the mechanisms for the above and NO-mediated impediments of antitumor effects of IL-2 therapy. Our results to date have shown the expression of endothelial type (e) NOS by tumor cells within spontaneous as well as transplanted C3H/HeJ mammary tumors is positively correlated with metastasis. Currently we are exploring the effects of downregulating eNOS gene on tumor cell behavior. We have further shown that endogenous as well as induced NO promoted invasiveness of a highly metastatic mammary tumor line C3L5. This was due to an upregulation of the invasion-promoting enzyme matrix metalloprotease (MMP)-2 and a downregulation of the MMP inhibitors TIMP-2 and TIMP-3. Finally, we have shown that NO induced by IL-2 therapy suppressed the activation of antitumor killer cells, which was abrogated by addition of NOS inhibitors. Thus NOS inhibitors may have a valuable role in cancer therapy.


Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE