Abstract 18273: Cardiomyocytes Inhibit the Growth of Lung and Breast Cancer Cells but Fail to Abrogate the Proliferation of Melanoma Cells
The adult heart is an organ resistant to primary cancer formation and secondary metastatic invasion. Rhabdomyosarcomas are rare and the majority of primary tumors are benign and restricted to the atria. Similarly, secondary invasion of cancer cells is not a common event. Despite the widespread diffusion of breast and lung cancer, intracardiac metastases are uncommon. However, skin melanoma cells have a particularly high propensity for cardiac seeding. In this study, we tested whether the interaction of cardiomyocytes and their miRs with lung (A549), breast (MCF7) and melanoma cancer cells (B16) differed, providing a molecular basis for the distinct invasive properties of these tumors in the heart. The in vitro growth rate of the three cancer cell lines was determined and found to be greater in A549 and B16 cells than in MCF7 cells. The expression of the muscle specific miR-1 and miR-133a was high in myocytes and barely detectable in A549, B16 and MCF7 cells. To determine whether miRs transfer from myocytes to cancer cells, the three cell types were co-cultured with myocytes for 4 days. The levels of miR-1 and miR-133a markedly increased in A549 and MCF7 cells, but failed to do so in B16 cells. To establish whether the increase in miR-1 and mi-R-133a in co-cultured cells was mediated by a paracrine mechanism, the level of these miRs was measured in microvesicles and exosomes. In all cases, miR-1 and miR-133a were detected in the microvesicles and exosomes, but their quantity was negligible in comparison with their respective intracellular content. Thus, lung and breast cancer cells are susceptible to miR transfer via gap junction channels, while melanoma cells are resistant to miR translocation. Importantly, the expression of connexin 43 was distributed on the surface of A549 and MCF7 cells but in B16 cells connexin 43 was seen in the intracellular compartment, with cytoplasmic and nuclear localization. Collectively, our results suggest that the transfer of miR-1 and mi-R-133a from cardiomyocytes to lung and breast cancer cells interferes with their engraftment and growth within the myocardium. Conversely, the impaired formation of gap junction channels between myocytes and B16 cells may offer an explanation for the propensity of melanoma cells to metastasize to the heart.
Author Disclosures: L. Graciotti: None. T. Hosoda: None. F. Sanada: None. G. Borghetti: None. C. Arranto: None. F. Valeriani: None. E. Wybieralska: None. B. Ogorek: None. M. Rota: None. P. Goichberg: None. P. Anversa: None. A. Leri: None.
- © 2014 by American Heart Association, Inc.