Background: The incidence of HIV infection is rising in women and even though its impact on breast cancer incidence is still under investigation, it is well assessed that patients with HIV infection present with more advanced stage and aggressive disease, and they also have poor chemotherapy tolerance. Vitamin D binding protein-macrophage activating factor (DBP-MAF) has been successfully used in immunotherapy of HIV-infected patients (J Med Virol 81:16-26, 2009). Since HIV infection and breast cancer can coexist in women, in this study we evaluated the effects of DBP-MAF on human breast cancer cell proliferation and tumour-induced angiogenesis. Methods: DBP-MAF was obtained from www.gcmaf.eu. Assessment of MCF-7 (human breast cancer) cell proliferation was determined by Calbiochem Rapid Cell Proliferation Kit. MCF-7 cells were also studied by scanning and conventional microscopy. MCF-7-induced angiogenesis was studied in chick embryo chorionallantoic membrane (CAM) assay. Results: DBP-MAF (0.4-40 ng/ml, incubated for 72 h) inhibited MCF-7 cell proliferation in a dose-dependent manner. Vitamin D also inhibited MCF-7 cell proliferation and the effects of vitamin D and DBP-MAF were additive. DBP-MAF-treated cells were significantly smaller and inhomogeneous as if processes of shrinkage had occurred. Cytoplasm and nucleus appeared irregular as if fragmented. Cellular debris could be observed as well as apoptotic bodies. Vimentin expression was reduced following DBP-MAF treatment. It is worth noting that increased vimentin expression is considered a hallmark of progression of breast cancer due to tumour cells losing their epithelial features and gaining mesenchymal properties. DBP-MAF inhibited MCF-7-induced neo-angiogenesis in CAM assay, another critical step in breast cancer progression. Conclusion: These results demonstrate that DBP-MAF, in addition to stimulating macrophages, directly inhibits human breast cancer cell growth in vitro. Therefore, administration of DBP-MAF to HIV-infected women could provide the dual benefit of immunotherapy of HIV infection and prevention of breast cancer progression (Abstract no. CDB269)
Vitamin D binding protein-macrophage activating factor directly inhibits proliferation of human breast cancer cells, vimentin expression and tumour-induced angiogenesis / S. Pacini; M. Ruggiero. - (2011), pp. 0-0. (Intervento presentato al convegno VI IAS Conference on HIV Pathogenesis, Treatment and Prevention tenutosi a Roma, Italy nel 17 - 20 Luglio 2011).
Vitamin D binding protein-macrophage activating factor directly inhibits proliferation of human breast cancer cells, vimentin expression and tumour-induced angiogenesis.
PACINI, STEFANIA;RUGGIERO, MARCO
2011
Abstract
Background: The incidence of HIV infection is rising in women and even though its impact on breast cancer incidence is still under investigation, it is well assessed that patients with HIV infection present with more advanced stage and aggressive disease, and they also have poor chemotherapy tolerance. Vitamin D binding protein-macrophage activating factor (DBP-MAF) has been successfully used in immunotherapy of HIV-infected patients (J Med Virol 81:16-26, 2009). Since HIV infection and breast cancer can coexist in women, in this study we evaluated the effects of DBP-MAF on human breast cancer cell proliferation and tumour-induced angiogenesis. Methods: DBP-MAF was obtained from www.gcmaf.eu. Assessment of MCF-7 (human breast cancer) cell proliferation was determined by Calbiochem Rapid Cell Proliferation Kit. MCF-7 cells were also studied by scanning and conventional microscopy. MCF-7-induced angiogenesis was studied in chick embryo chorionallantoic membrane (CAM) assay. Results: DBP-MAF (0.4-40 ng/ml, incubated for 72 h) inhibited MCF-7 cell proliferation in a dose-dependent manner. Vitamin D also inhibited MCF-7 cell proliferation and the effects of vitamin D and DBP-MAF were additive. DBP-MAF-treated cells were significantly smaller and inhomogeneous as if processes of shrinkage had occurred. Cytoplasm and nucleus appeared irregular as if fragmented. Cellular debris could be observed as well as apoptotic bodies. Vimentin expression was reduced following DBP-MAF treatment. It is worth noting that increased vimentin expression is considered a hallmark of progression of breast cancer due to tumour cells losing their epithelial features and gaining mesenchymal properties. DBP-MAF inhibited MCF-7-induced neo-angiogenesis in CAM assay, another critical step in breast cancer progression. Conclusion: These results demonstrate that DBP-MAF, in addition to stimulating macrophages, directly inhibits human breast cancer cell growth in vitro. Therefore, administration of DBP-MAF to HIV-infected women could provide the dual benefit of immunotherapy of HIV infection and prevention of breast cancer progression (Abstract no. CDB269)
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