Abstract 4224: Differential effect of iodine on the implantation and metastatic potential of xenografts from two different human breast cancer cell lines
Authors: Irasema Mendieta, Elvira Nunez-Anita, Guadalupe Delgado, Carmen Aceves
Journal: Cancer Research (2011)

Abstract In spite of advances in therapeutics and screening programs, breast cancer metastasis to vital organs (brain, lungs, and bone) is the main cause of death of the patients diagnosed with this disease. The process of metastasis requires a series of steps including the expression of several molecular factors that permit the invasion, angiogenesis, and colonization of other organs. Data generated in different laboratories including ours have shown that molecular iodine (I2) exerts a potent antineoplastic effect on in vitro and in vivo cancer models. Molecular analyses of this effect in methylnitrosourea-induced mammary cancer showed that, besides activating the Bax-caspase apoptotic pathway, I2 also interfered with the metastatic potential by decreasing the expression of urokinase-type plasminogen activator (uPA) and vascular endothelial growth factor (VEGF), proteins intimately related to invasion and vascularization, respectively. To determine the role of I2 in the implantation and metastatic potential of human mammary cancer, we used xenografts of two human breast cancer cell lines with different metastatic potential (MCF-7 and MDA-MB231). Female athymic homozygotic (Foxn1 nu/nu) mice (8 weeks old) were injected subcutaneously with 5 million parental cells of each cell line in 50 µl PBS and 50 µl matrigel. Drinking water for the control group was deionized water, which was supplemented with 0.025% I2 for the iodine group. All animals were monitored for 6 weeks at weekly intervals for the development of tumors. Tumor sizes were calculated by the ellipsoid formula, proliferation rate was measured by Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry, and the metastatic potential was estimated by uPA activity (enzymatic assay). The results showed that the I2 supplement decreases the implantation capacity (incidence), tumoral growth, and cell proliferation of both cell lines, MDA-MB231 (20%; 0.18 ± 0.08 cm3; 34.8% PCNA-positive cells/field) and MCF-7 (50%; 0.5 ± 0.07 cm3; 34.3% PCNA-positive cells/field) in comparison with the control (95.1%; 2.2 ± 0.3 cm3; 42.8% PCNA-positive cells/field). In contrast, I2 decreased the metastatic potential (uPA activity) only in those tumors that had been generated from MCF-7 (32 ± 5.6 vs 52 ± 2.8 IU/mg protein control). In conclusion, our data suggest that I2 supplementation interferes primarily with the implantation and proliferation of mammary cancer cells, but it may be ineffective in decreasing the metastatic potential of those cancer cells with a more aggressive phenotype. Acknowledgements to Biol. Felipe Ortíz, Dr. Laura Vega for the technical support, and Dr. Dorothy Pless for proofreading. Study partially supported by UNAM/DGAPA IN201210 and CONACYT 78955. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4224. doi:10.1158/1538-7445.AM2011-4224