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1.
Arch Gynecol Obstet ; 295(4): 987-995, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28239742

RESUMO

PURPOSE: Stroma-derived factor-1 (SDF-1) and its receptor C-X-C chemokine receptor-4 (CXCR4) are involved in human endometrial carcinoma (EC) progression. CXCR7 is another important receptor of SDF-1 and has a higher affinity with SDF-1 compared with that of CXCR4. This paper aims to study the effects of the SDF-1/CXCR7 axis on the growth and invasion ability of EC cells. METHODS: CXCR7 expression was evaluated by quantitative RT-PCR, immunohistochemistry, immunocytochemistry and Western blotting in EC cell lines and 30 cases of primary EC tissue from patients. EC cell line proliferation and migration were assessed following knockdown of CXCR7 by MTT and transwell assays. RESULTS: The results showed that CXCR7 was highly expressed at both mRNA and protein levels in the EC cells and tissue. siCXCR7 effectively silenced CXCR7 in Ishikawa and AN3CA cells. Treatment with 17ß-oestradiol (17ß-E2) significantly increased the levels of CXCR7 and SDF-1 in Con, siCon and siCXCR7 treated Ishikawa. siCXCR7 persistently inhibited CXCR7 expression, even in cells treated with 17ß-E2. Moreover, in vitro functional analyses, silencing CXCR7 resulted in decreased proliferation in Ishikawa and AN3CA cells. Treatment with 17ß-E2 and SDF-1 significantly promoted the growth and migration in siCon treated Ishikawa and AN3CA. Interestingly, in response to 17ß-E2 and SDF-1 stimulation, siCXCR7 continuously inhibited the growth and invasion of Ishikawa and AN3CA cells. CONCLUSION: Our results indicate that SDF-1/CXCR7 plays a positive role in the proliferation and invasion of EC cells. CXCR7 inhibition treatment may provide a promising strategy for anti-tumour therapy for EC.


Assuntos
Proliferação de Células/genética , Quimiocina CXCL12/fisiologia , Neoplasias do Endométrio/patologia , Células Endoteliais/patologia , Invasividade Neoplásica/genética , Receptores CXCR/fisiologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimiocina CXCL12/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Estradiol/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , RNA Mensageiro/metabolismo , Receptores CXCR/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
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