RESUMO
BACKGROUND/AIM: The aim of this study was to elucidate the relationship between the progression of bladder cancer (BCa) and TLR4 expression. MATERIALS AND METHODS: The relationship between TLR4 expression and prognosis of BCa patients was analyzed using a publicly available database and immunohistochemical staining of clinical samples. The effect of TLR4 knockdown was also examined on the invasive capabilities of BCa cells. Finally, to investigate the biological function of TLR4, the gene expression profile of TLR4-depleted BCa cells was analyzed by microarray analysis. RESULTS: Expression of TLR4 was inversely associated with prognosis of patients with invasive BCa, and depletion of TLR4 significantly enhanced the invasive capability of BCa cells. Gene expression profiling revealed that depletion of TLR4 led to high expression of epithelial differentiation genes. Furthermore, expression of TLR4 was found to be extremely low in areas of squamous differentiation. CONCLUSION: Low TLR4 expression was correlated with tumor progression.
Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Receptor 4 Toll-Like/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Diferenciação Celular , Linhagem Celular Tumoral , Biologia Computacional , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Interferente Pequeno/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To clarify the invasive mechanisms of muscle-invasive bladder cancer (BCa) would be useful for the determination of appropriate treatment strategies. We previously showed that hepatocyte growth factor (HGF)-MET signaling is correlated with invasiveness of BCa cells. Here, we investigated the effects of the MET inhibitor, cabozantinib (XL184), on BCa cells. METHODS: We first conducted Western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively. Invasion assays were performed using the xCELLigence system. Additionally, to investigate the biological function of HGF-MET signaling, we analyzed gene expression profiles and performed real-time polymerase chain reaction analyses of 5637 cells that were cultivated with or without HGF stimulation, with or without cabozantinib. RESULTS: MET was highly expressed in 4 of 5 BCa cell lines, and 5637 and T24 cells showed especially high protein expression of MET. Cabozantinib suppressed cell proliferation and invasion (cell index; mock, 1.49 vs HGF, 2.26 vs HGF + XL184, 1.47, P < .05). Gene expression profile analysis indicated that matrix metalloproteinase 1 (MMP1) was significantly elevated at the mRNA level with addition of HGF. Moreover, cabozantinib suppressed HGF-induced MMP1 expression in 5637 T24 cells. CONCLUSIONS: These data indicate that cabozantinib suppressed MMP1 expression by blocking HGF-MET signaling and that HGF-MET-MMP1 signaling is involved in the invasiveness and proliferation of BCa cells. These results suggest that cabozantinib might prove useful for future treatment of muscle-invasive BCa.
Assuntos
Anilidas/farmacologia , Regulação Neoplásica da Expressão Gênica , Fator de Crescimento de Hepatócito/genética , Metaloproteinase 1 da Matriz/genética , Proteínas Proto-Oncogênicas c-met/genética , Piridinas/farmacologia , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária/metabolismo , Western Blotting , Contagem de Células , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento de Hepatócito/biossíntese , Humanos , Metaloproteinase 1 da Matriz/biossíntese , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Análise Serial de Proteínas , Proteínas Proto-Oncogênicas c-met/biossíntese , RNA Neoplásico/genética , Receptores Proteína Tirosina Quinases , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismoRESUMO
A case of intra-abdominal testis with loop-like epididymis and intra-canalicular vas and vessels is presented. A 3-year-old male with left impalpable testis since birth was admitted to our department. Physical examination and ultrasonography were inconclusive. Laparoscopy revealed a small left abdominal testis with surrounding adhesions close to the left-obliterated umbilical artery. The vas deferens and spermatic vessels were entering into the internal inguinal ring. The processus vaginalis was patent. At inguinal exploration the testis was atrophic and the epididymis was loop-like, joining the vas deferens in the inguinal canal. The spermatic vessels continued to the atrophic testis in a loop-like manner. The testis, epididymis and the vas deferens were removed. Histopathological examination of the testis revealed Sertoli cells only. If inguinal exploration had been performed without laparoscopy, the presence of the vas deferens and spermatic vessels in the inguinal canal with the absence of the testis could have been misdiagnosed as vanishing testis. Abdominal testis would thus have been missed, with increased risk of complications, particularly malignancy.