Influence of polyamines on in vitro and in vivo features of aggressive and metastatic behavior by human breast cancer cells.

摘要: Increased cellular activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine (PA) synthesis, is an independent adverse prognostic factor for overall survival human breast cancer [4], thus suggesting important role PA tumor progression. The experiments presented here were designed to investigate invasion metastasis, using highly aggressive MDA-MB-435 MDA-MB-231 cell lines. Administration α-difluoromethylornithine (DFMO), irreversible inhibitor ODC, significantly reduced, a dose-dependent manner, invasiveness matrigel both cells by ∼70%. DFMO treatment also inhibited (P<0.0001) `stellate' colony formation (an indicator phenotype) plated outgrowth assay. (2% drinking water) reduced growth rate lines implanted orthotopically nude mice. To evaluate metastasis while minimizing effects on proliferation, DFMO-treated mice sacrificed later allow their tumors reach same size control most striking finding was that DFMO, ineffective reducing local invasion, nearly totally abolished (P=0.0152) pulmonary bearing xenografts. These results support promoting aggressiveness, particularly with regard development distant metastasis. Furthermore, data suggest involvement distal metastatic cascade.