Objectives: It was demonstrated that vitamin D binding protein-derived macrophage activating factor (GcMAF) decreases serum alpha-N-acetyl galactosaminidase (nagalase) in breast cancer patients; decrease of nagalase was associated with significant improvement of clinical conditions (Int J Cancer. 2008 Jan 15;122(2):461-7). Since nagalase is both an index of immune suppression and of tumour burden, we studied the direct effects of GcMAF on a human breast cancer cell line (MCF-7), and we compared the effects in vitro with those observed in breast cancer patients. Methods: The effects of GcMAF on proliferation, morphology, vimentin expression and angiogenesis were studied by cell proliferation assay, phase-contrast microscopy, immunohistochemistry and western blotting, and chorioallantoic membrane assay. Results: GcMAF inhibited human breast cancer cell proliferation and cancer cellstimulated angiogenesis. Furthermore, GcMAF significantly reduced vimentin expression, indicating a reversal of the epithelial/mesenchymal transition, a hallmark of human breast cancer progression. These results were consistent with the preliminary observation of two breast cancer patients. The two patients (age 65 and 62) presented with elevated levels of nagalase; 1.70 and 5.60 nM/min/mg respectively (normal values below 0.65). After 8 and 17 months of weekly intravenous administration of 100 ng GcMAF respectively, nagalase levels decreased to 0.60 and 1.10, thus indicating a decrease of the tumour burden. Conclusions: These results support the hypothesis that the effects of GcMAF in cancer patients can be ascribed to different biological properties of the molecule that, in addition to stimulating macrophages, inhibits cancer cell proliferation, migration and metastatic potential as well as tumour-induced angiogenesis.
Vitamin D binding protein-derived macrophage activating factor inhibits human breast cancer cell proliferation and decreases alpha-N-acetyl galactosaminidase in breast cancer patiens
G. Morucci;J.J.V. Branca;
2013-01-01
Abstract
Objectives: It was demonstrated that vitamin D binding protein-derived macrophage activating factor (GcMAF) decreases serum alpha-N-acetyl galactosaminidase (nagalase) in breast cancer patients; decrease of nagalase was associated with significant improvement of clinical conditions (Int J Cancer. 2008 Jan 15;122(2):461-7). Since nagalase is both an index of immune suppression and of tumour burden, we studied the direct effects of GcMAF on a human breast cancer cell line (MCF-7), and we compared the effects in vitro with those observed in breast cancer patients. Methods: The effects of GcMAF on proliferation, morphology, vimentin expression and angiogenesis were studied by cell proliferation assay, phase-contrast microscopy, immunohistochemistry and western blotting, and chorioallantoic membrane assay. Results: GcMAF inhibited human breast cancer cell proliferation and cancer cellstimulated angiogenesis. Furthermore, GcMAF significantly reduced vimentin expression, indicating a reversal of the epithelial/mesenchymal transition, a hallmark of human breast cancer progression. These results were consistent with the preliminary observation of two breast cancer patients. The two patients (age 65 and 62) presented with elevated levels of nagalase; 1.70 and 5.60 nM/min/mg respectively (normal values below 0.65). After 8 and 17 months of weekly intravenous administration of 100 ng GcMAF respectively, nagalase levels decreased to 0.60 and 1.10, thus indicating a decrease of the tumour burden. Conclusions: These results support the hypothesis that the effects of GcMAF in cancer patients can be ascribed to different biological properties of the molecule that, in addition to stimulating macrophages, inhibits cancer cell proliferation, migration and metastatic potential as well as tumour-induced angiogenesis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
