RESUMO
Platelets play a role in tumor angiogenesis and growth and are the main transporters of several angiogenesis regulators. Here, we aimed to determine the levels of angiogenesis regulators and epithelial-mesenchymal transition factors sequestered by circulating platelets in breast cancer patients and age-matched healthy controls. Platelet pellets (PP) and platelet-poor plasma (PPP) were collected by routine protocols. Vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), thrombospondin-1 (TSP-1), platelet factor 4 (PF4), and transforming growth factor-ß1 (TGF-ß1) were measured by enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF (2.1 pg/10(6) platelets versus 0.9 pg/10(6) platelets, P < 0.001), PF4 (21.2 ng/10(6) platelets versus 10.2 ng/10(6) platelets, P < 0.001), PDGF-BB (42.9 pg/10(6) platelets versus 19.1 pg/10(6) platelets, P < 0.001), and TGF-ß1 (15.3 ng/10(6) platelets versus 4.3 ng/10(6) platelets, P < 0.001) differed in the PP samples of cancer and control subjects. In addition, protein concentrations were associated with clinical characteristics (P < 0.05). Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF-BB, and TGF-ß1, suggesting a possible target for early diagnosis. VEGF, PDGF, and TGF-ß1 concentrations in platelets may be associated with prognosis.
Assuntos
Biomarcadores Tumorais/genética , Plaquetas/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Expressão Gênica , Adulto , Idoso , Becaplermina , Biomarcadores Tumorais/metabolismo , Plaquetas/patologia , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica , Fator Plaquetário 4/genética , Fator Plaquetário 4/metabolismo , Proteínas Proto-Oncogênicas c-sis/genética , Proteínas Proto-Oncogênicas c-sis/metabolismo , Trombospondina 1/genética , Trombospondina 1/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
MicroRNAs (miRNAs), as a class of naturally occurring small non-coding RNAs, play profound and pervasive roles in cancer initiation and progression. Extensive decrease in miRNA levels are frequently observed in human cancers, indicating that miRNAs may function intrinsically in tumor suppression. However, the underlying mechanisms of miRNA interactions with cellular pathways are still unclear. The expression of miR-34b in non-small cell lung cancer (NSCLC) tissues was detected using quantitative real-time PCR. The relations between miR-34b expression levels and pathological stage or lymph node metastasis were assessed using the Spearman correlation test. For in vitro studies, lung cancer cells were transfected with double stranded synthetic miRNA mimics (syn-hsa-miR-34b miScript miRNA) and scrambled controls. Immunohistochemistry was used to validate the related downstream proteins of miR-34b. The expression of miR-34b was lower in NSCLC tissues compared to that in pericarcinous tissues of lung cancer. Additionally, the Spearman correlation test showed that lower miR-34b expression was correlated with higher lymph node metastasis. In vitro gain-of-function experiments indicated that miR-34b suppressed cell proliferation by inducing cell apoptosis. IHC results showed association between lower miR-34b and overexpression of phospho-Met, p53 (phospho S392) and Mdm2. Consistent with the opposing correlation between the expression of miR-34b and lymph node metastasis in NSCLC, miR-34b may play an important role in NSCLC progression. Furthermore, miR-34b downregulates Met, with subsequent changes of downstream p53 (phospho S392) and Mdm2, and inversely p53 upregulates miR-34b in a feedback loop, which provides new insights into the roles of miR-34 family members in the regulation of signaling pathways of NSCLC.