RESUMO
Tumor microenvironment is an important promoter of tumorigenesis in all forms of breast cancer and has been associated with the risk of metastasis in the different breast cancer subtypes including the more frequent luminal subtypes that encompass 60% of cancer patients. Adhesive properties of endothelial cells (ECs) are strikingly affected during cancer cell dissemination and are related to functional changes of adhesion receptors. The contribution of tumor secreted factors to tumorEC adhesion represents a therapeutic opportunity for breast cancer metastasis. Conditioned medium (CM) of tumor cells can be used as a model to study the role of the secreted molecules to the tumor microenvironment. We explored transcriptomic changes associated to a proadhesive phenotype in primary human umbilical vein endothelial cells (HUVECs) treated with CM of the breast cancer cell line ZR75.30 or with TNF for 3 h. Selected genes were used to validate the microarray through RTqPCR. The bioinformatic analysis identified NFκB as the main regulator of the pro-adhesive phenotype and this was confirmed by pharmacological inhibition of NFκB pathway with BAY 117085. The changes induced by ZR75.30CM mimic those promoted by TNF and display changes in the expression of genes related to inflammatory response, wound healing, extracellular matrix, cytokines, metabolism and cell communication. Despite the abundance of GCSF, IL8, IL6 and VEGF in the ZR75.30CM and the confirmed activation of STAT3 and VEGFR2 pathways, our results suggest dominance of NFκB as a central controller of the transcriptomic response of ECs to breast cancer cells leading to expression of cell adhesion receptors.
Assuntos
Neoplasias da Mama/patologia , Adesão Celular/fisiologia , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/patologia , NF-kappa B/metabolismo , Transcriptoma , Western Blotting , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , NF-kappa B/genética , Metástase Neoplásica , Fenótipo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais CultivadasRESUMO
Cardiovascular disease (CVD) is a major cause of mortality in the Republic of Mexico, and metabolic syndrome, a complex of CVD risk factors, is increasingly prevalent. To date, however, there have been few studies of the genetic epidemiology of metabolic syndrome in Mexico. As a first step in implementing the GEMM Family Study, a large, multicenter collaborative study, we recruited 375 individuals in 21 extended families, without ascertainment on disease, at 9 medical institutions across Mexico. Participants were measured for anthropometric (stature, weight, waist circumference) and hemodynamic (blood pressure, heart rate) phenotypes; glucose, cholesterol, and triglyceride levels were measured in fasting blood. Variance components-based quantitative genetic analyses were performed using SOLAR. All phenotypes except diastolic blood pressure were significantly heritable. Consistent with the definition of metabolic syndrome, many phenotypes exhibited significant environmental correlation, and significant genetic correlations were found between measures of adiposity and fasting glucose and fasting triglyceride levels. These preliminary data represent the first heritability estimates for many of these phenotypes in the Republic of Mexico and indicate that this study design offers excellent power for future gene discovery relative to metabolic disease.
Assuntos
Doenças Cardiovasculares/genética , Genética Populacional/métodos , Síndrome Metabólica/genética , Fenótipo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , Pressão Sanguínea/genética , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , México/epidemiologia , Pessoa de Meia-IdadeRESUMO
Con el objeto de reconocer algunos aspectos que intervienen en la susceptibilidad vascular de pacientes con hipertensión asociada a embarazo se efectuaron determinaciones de Ca2+, Mg2+, fósforo y creatinina en el plasma de pacientes con embarazo normal y preeclampsia. Destacó que estas últimas exhibieron niveles bajos de Ca2+ y elevados de Mg2+ diferentes (p=<0.01) a las gestantes normales, que persistieron aún después del parto. No se registrarom cambios sensibles en las concentraciones de fósforo. Los niveles de creatinina sérica se encontraron elevados en los pacientes con hipertensión, obteniéndose una correlación positiva con las cantidades de fósforo circulante. En el embarazo normal se registró un balance adecuado entre Ca2+ y Mg2+. Se concluye que las modificaciones en los niveles de cationes observados en nuestro estudio pueden contribuir a la heperreactividad vascular de pacientes con hipertensión gestacional
