Reduction of tumor angiogenesis induced by desmopressin in a breast cancer model.

ABSTRACT

Desmopressin (DDAVP), a synthetic peptide analog of vasopressin, is a safe antidiuretic and hemostatic compound that acts as a selective agonist for the vasopressin V2 membrane receptor. It is known that DDAVP can inhibit progression of residual metastatic cells and also improves chemotherapy effects in preclinical breast cancer models. Here, we explored the effects of DDAVP on tumor angiogenesis using the aggressive F3II mammary carcinoma in syngeneic Balb/c mice. Intravenous administration of the compound (2 µg/kg) markedly decreased vascularization of growing subcutaneous tumors, as well as inhibited the early angiogenic response around intradermal inoculation sites. In vitro studies confirmed the presence of vasopressin V2 receptors on F3II cells and a modest antiproliferative activity of DDAVP. Interestingly, conditioned media from F3II monolayers exposed to low doses of DDAVP (100 nM) significantly increased angiostatin formation in the presence of purified plasminogen. Such increase was associated with an enhancement of tumor-secreted urokinase-type plasminogen activator, suggesting the proteolytic conversion of plasminogen to angiostatin in vitro. Similar results were observed with the MCF-7 human breast carcinoma, a cell line known to express the vasopressin V2 receptor. No direct effects of DDAVP (100 nM­1 µM) were found on capillary-like tube formation by human microvascular cells HMVEC. Our studies showed that DDAVP induces anti-angiogenic effects that may be associated with the generation of angiostatin by tumor cells. Further preclinical studies with DDAVP and other vasopressin analogs are warranted to determine their potential in cancer management.