RESUMO
Microvesicles (MVs) are secreted by multiple types of tumor cell and are involved in tumor progression and metastasis. The aim of the present study was to explore the effects of MVs derived from salivary adenoid cystic carcinoma (SACC) and to investigate their potential involvement in the pathogenesis of perineural invasion of SACC. MVs were isolated from ACCs cells, and differential gene expression profiles of these MVs were compared with their donor cells to speculate on their biological functions. Several candidate genes were validated using reverse transcription-quantitative polymerase chain reaction analysis. The effects of ACCs MVs on rat Schwann cells (RSC96 cells), which are the principal glia of the peripheral nervous system, were then evaluated by phospho-antibody array performed on RSC96 cells transduced with ACCs MVs. The results indicated that ACCs cells may produce MVs. Microarray-based expression profiles between ACCs cells and their MVs identified 1,355 genes involved in cell adhesion, development and the regulation of apoptosis. In addition, the extracellular signal-regulated protein kinase signal pathway in RSC96 cells may be induced by ACCs-derived MVs. These results may help to elucidate the mechanisms underlying perineural invasion in SACC, and to determine a promising anti-tumor biological therapeutic target.
RESUMO
CXC chemokine receptor 4 (CXCR4) is involved in many human malignant tumors and plays an important role in tumor growth and metastasis. To explore the effects of CXCR4 expression on the malignant cells of oral squamous cell carcinoma (OSCC), Tca8113 and SCC-9 cell lines, as well as their xenograft models, of nude mice were used to detect cancer cell proliferation alteration. This study also examined the corresponding molecular mechanism after CXCR4 knockdown using a recombinant lentiviral vector expressing small interference RNA (siRNA) for CXCR4. RNA interference-mediated knockdown of CXCR4 in highly aggressive (Tca8113 and SCC-9) tumor cells significantly inhibited the proliferation of the two cell lines in vitro and in vivo. The expression levels of >1,500 genes involved in cell cycle, apoptosis, and multiple signaling pathways were also altered. These results provide new evidence of CXCR4 as a promising tumor gene therapeutic target.
Assuntos
Apoptose/genética , Carcinoma de Células Escamosas/terapia , Pontos de Checagem do Ciclo Celular/genética , Neoplasias Bucais/terapia , Interferência de RNA , Receptores CXCR4/antagonistas & inibidores , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Análise por Conglomerados , Expressão Gênica , Perfilação da Expressão Gênica , Inativação Gênica , Vetores Genéticos/genética , Humanos , Antígeno Ki-67/metabolismo , Lentivirus/genética , Camundongos , Camundongos Nus , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores CXCR4/genética , Transdução Genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: The purpose of this study was to examine the expression of human major histocompatibility complex-I at different degrees of dysplasia leukoplakia, and to investigate local immune status and discuss their associations with oral leukoplakia. METHODS: The monoclonal antibody of MHC class I antigen was employed in this study. There were 55 oral leukoplakias, 31 primary oral squamous cell carcinomas and 28 histologically normal oral epithelia were detected for the presence of the MHC class I molecule by using immunohistochemistry method. RESULTS: The MHC class I antigen expression of the severe dysplasia and oral squamous cell carcinoma was significantly lower than that of the normal epithelia (P < 0.05). But their expression did not show statistically difference between the normal epithelia and other groups of oral leukoplakia (P > 0.05). CONCLUSION: The expression levels of the MHC class I antigen is reduced in oral leukoplakia, particularly in severe dysplasia oral leukoplakia, it is relevant to the degree of dysplasia.