RESUMO
Although studies have suggested organochlorine pesticides (OCPs) exposure increased the risk of epithelial ovarian cancer, the mechanisms underlying its potential tumorigenic effects in the human ovary are not well understood. In this study, we investigated the impact of dichlorodiphenyldichloroethylene (DDE), endosulfan, and heptachlor exposure on epithelial cadherin (E-cadherin) and proinflammatory mediators in human ovary surface epithelial (HOSE) cells. We found that DDE, endosulfan, and heptachlor exposure resulted in epithelial differentiation accompanied by upregulation of E-cadherin expression and overexpression of proinflammatory cytokines (TNFα, IL-1ß, and IL-6) in HOSE cells. The epithelial differentiation may accelerate HOSE cells to inclusion body formation, a common site for ovarian cancer initiation and persistent exposure to OCPs creates a chronic inflammatory microenvironment that may promote the neoplastic transformation of HOSE cells within the inclusion cyst.
Assuntos
Hidrocarbonetos Clorados , Praguicidas , Humanos , Feminino , Diclorodifenil Dicloroetileno/análise , Diclorodifenil Dicloroetileno/metabolismo , Endossulfano/toxicidade , Ovário/metabolismo , Mediadores da Inflamação/metabolismo , Hidrocarbonetos Clorados/toxicidade , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/metabolismo , Praguicidas/toxicidade , Praguicidas/metabolismo , Heptacloro/análise , Heptacloro/metabolismo , Células Epiteliais/metabolismo , Caderinas/metabolismoAssuntos
Carcinoma Epitelial do Ovário/genética , Citocromo P-450 CYP1A1/genética , Glutationa Transferase/genética , Neoplasias Ovarianas/genética , Praguicidas/sangue , Adulto , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/induzido quimicamente , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Hidrocarbonetos Clorados/sangue , Hidrocarbonetos Clorados/toxicidade , Inativação Metabólica/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/induzido quimicamente , Praguicidas/toxicidade , Polimorfismo GenéticoRESUMO
Metastasis accounts for the majority of cancer-associated mortality and renders the targeted therapy fruitless in the patients of breast cancer. Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF-C) are thought to be involved in tumor progression and metastasis. The aim of this study was to investigate the expression of MMP-9 and VEGF-C at both mRNA and protein levels in breast cancer and to correlate with lymph node metastasis and other clinicopathological characteristics. Biopsy specimens (N = 100) of breast cancer & benign breast disease (N = 100) were investigated for the mRNA expression of MMP-9 and VEGF-C by Real-time PCR and Protein expression by Western blot. Elevated levels of MMP-9 (p < 0.001) and VEGF-C (p < 0.001) expression were detected in breast cancer with corresponding to benign breast disease. Additionally, we found significantly increased levels of MMP-9 and VEGF-C in node-positive group with respect to node-negative group. Moreover, the levels of MMP-9 were significantly increased in larger tumor size (T3/T4) (p < 0.05) as compared to smaller size (T1/T2), which suggests that MMP-9 plays an important role in the progression of breast cancer. VEGF-C expression was associated with the TNM stage of tumor (p < 0.05). Further, a significant positive correlation was established between the mRNA levels of these two genes (p < 0.001). However, we could not obtain any significant correlation between expression of these genes with other clinicopathological parameters like tumor grade, age, menopausal status, and receptor status like ER, PR, and Her2. This study suggests that the high expression of MMP-9 and VEGF-C could act as markers for the tumor presence in breast cancer. In addition, this study recommends that expression of MMP-9 and VEGF-C was significantly associated with lymph node status and may provide valuable diagnosis of lymph node metastasis in breast cancer patients. Further, MMP-9 expression was associated with the tumor size and VEGF-C expression was correlated with the staging of the tumor, although no association was observed with other clinicopathological variables.