RESUMO
Tumors have high requirements in terms of nutrients and oxygen. Angiogenesis is the classical mechanism for vessel formation. Tumoral vascularization has the function of nourishing the cancer cells to support tumor growth. Vasculogenic mimicry, a novel intratumoral microcirculation system, alludes to the ability of cancer cells to organize in three-dimensional (3D) channel-like architectures. It also supplies the tumors with nutrients and oxygen. Both mechanisms operate in a coordinated way; however, their functions in breast cancer stem-like cells and their regulation by microRNAs remain elusive. In the present study, we investigated the functional role of microRNA-204 (miR-204) on angiogenesis and vasculogenic mimicry in breast cancer stem-like cells. Using flow cytometry assays, we found that 86.1% of MDA-MB-231 and 92% of Hs-578t breast cancer cells showed the CD44+/CD24- immunophenotype representative of cancer stem-like cells (CSCs). The MDA-MB-231 subpopulation of CSCs exhibited the ability to form mammospheres, as expected. Interestingly, we found that the restoration of miR-204 expression in CSCs significantly inhibited the number and size of the mammospheres. Moreover, we found that MDA-MB-231 and Hs-578t CSCs efficiently undergo angiogenesis and hypoxia-induced vasculogenic mimicry in vitro. The transfection of precursor miR-204 in both CSCs was able to impair the angiogenesis in the HUVEC cell model, which was observed as a diminution in the number of polygons and sprouting cells. Remarkably, miR-204 mimics also resulted in the inhibition of vasculogenic mimicry formation in MDA-MB-231 and Hs-578t CSCs, with a significant reduction in the number of channel-like structures and branch points. Mechanistically, the effects of miR-204 were associated with a diminution of pro-angiogenic VEGFA and ß-catenin protein levels. In conclusion, our findings indicated that miR-204 abrogates the angiogenesis and vasculogenic mimicry development in breast cancer stem-like cells, suggesting that it could be a potential tool for breast cancer intervention based on microRNA replacement therapies.
RESUMO
Es preocupante el impacto que las actividades laborales pueden tener en eldesarrollo y calidad de vida de los menores trabajadores, especialmentecuando estas actividades inician desde temprana edad. Los menores trabajadores en Toluviejo realizan diferentes actividades económicas, participando, entre otras, en la explotación de rocas calcáreas desde los 7 años. Con el objetivo de conocer y comparar la calidad de vida en salud y la salud mental positiva en los menores que trabajan con los que no lo hacen, seseleccionaron intencionalmente 191 menores del colegio del pueblo de loscuales el 18% indicaron trabajar en su tiempo libre. Los resultados arrojaronindicadores más bajos en los menores trabajadores, pero con resultadospoco significativos, lo cual indica que más que el trabajo, el problemamayor son las precarias condiciones en las que viven los menores.
The impact that the labor activities can have in the development and qualityof life of the working minors is worrisome, especially when these activities initiate from early age. The working minors in Toluviejo realise different economic activities, participating, among others, in the calcareous rock operation since they were 7 years old. With the aim of knowing and comparing the quality of life in health and the positive mental health in the minors who work with minors who do not do it, were intentionally selected 191 minorsof the school of the town of which 18% indicated to work in their free time.The results threw lower indicators in the working minors, but with littlesignificant results, which indicates that more than the work, the greaterproblem is the precarious conditions in which the minors live.