AIM To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS Western blotting was used to d...AIM To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells(HUVECs) were determined by enzyme-linked immunosorbent assay,and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/m TOR signaling by CXCL12 involved in the metastatic process of colon cancer.RESULTS CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration(P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells(P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/m TOR pathway.CONCLUSION Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells,and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/m TOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer.展开更多
AIM:To evaluate the expression of C-X-C motif chemokine receptor 4(CXCR4)and its signaling cascades,which were previously identified as a key factor for cancer cell progression and metastasis,in cholangiocarcinoma cel...AIM:To evaluate the expression of C-X-C motif chemokine receptor 4(CXCR4)and its signaling cascades,which were previously identified as a key factor for cancer cell progression and metastasis,in cholangiocarcinoma cell lines.METHODS:The expression of CXCR4 and its signaling cascades were determined in the cholangiocarcinoma cell lines(RMCCA1 and KKU100)by Western blotting.The invasion assays and the detection of actin polymerization were tested in these cholangiocarcinoma cells treated with CXC chemokine ligand-12(CXCL12).RESULTS:Expression of CXCR4 was detected in both cholangiocarcinoma cell lines and activation of CXCR4 with CXCL12 triggered the signaling via the extracellular signal-regulated kinase-1/2(ERK1/2)and phosphoinositide 3-kinase(PI3K)and induction of cholangiocarcinoma cell invasion,and displayed high levels of actin polymerization.Addition of CXCR4 inhibitor(AMD3100)abrogated CXCL12-induced phosphorylation of MEK1/2 and Akt in these cells.Moreover,treatment with MEK1/2 inhibitor(U0126)or PI3K inhibitor(LY294 002)also attenuated the effect of CXCL12-induced cholangiocarcinoma cell invasion.CONCLUSION:These results indicated that the activation of CXCR4 and its signaling pathways(MEK1/2 and Akt)are essential for CXCL12-induced cholangiocarcinoma cell invasion.This rises Implications on a potential role for the inhibition of CXCR4 or its signal cascades in the treatment of cholangiocarcinoma.展开更多
Objective The expression of CXCL12(stromal cell-derived factor-1)-CXCR4(chemokine receptors-4) in osteosarcoma and its role in angiogenesis were examined.Methods The expression of CXCR4 and CXCL12 in 40 cases of osteo...Objective The expression of CXCL12(stromal cell-derived factor-1)-CXCR4(chemokine receptors-4) in osteosarcoma and its role in angiogenesis were examined.Methods The expression of CXCR4 and CXCL12 in 40 cases of osteosarcoma was detected by immunohistochemistry and real-time fluorescence quantitative PCR.The expression of CD34 in osteosarcoma was detected by immunohistochemistry.Morphometric image analysis was performed to measure microvessel density(MVD).Additionally,the relationship between CXCL12 and CXCR4 expression and MVD of osteosarcoma and pulmonary metastasis were analyzed.Results The positive rates of CXCL12 and CXCR4 protein expression in osteosarcoma were 40.0%(16/40) and 60.0%(24/40),respectively.Fluorescence quantitative real-time PCR indicated that the expression level of CXCR4 m RNA in pulmonary metastatic osteosarcoma was higher than that in nonpulmonary metastatic osteosarcoma(P < 0.01).The level of MVD in pulmonary metastatic osteosarcoma was higher than that in non-pulmonary metastatic osteosarcoma(P < 0.01).Conclusion The expression level of CXCR4 was significantly associated with pulmonary metastasis and angiogenesis of osteosarcoma.展开更多
基金Supported by National Natural Science Foundation of China,No.81260325(to Ma JC)
文摘AIM To investigate the underlying mechanism by which CXCL12 and CXCL6 influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. METHODS Western blotting was used to detect the expression of CXCL12 and CXCL6 in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and CXCL6 on proliferation and invasion of colon cancer cells and human umbilical vein endothelial cells(HUVECs) were determined by enzyme-linked immunosorbent assay,and proliferation and invasion assays. The angiogenesis of HUVECs through interaction with cancer cells and stromal cells was examined by angiogenesis assay. We eventually investigated activation of PI3K/Akt/m TOR signaling by CXCL12 involved in the metastatic process of colon cancer.RESULTS CXCL12 was expressed in DLD-1 cancer cells and fibroblasts. The secretion level of CXCL6 by colon cancer cells and HUVECs were significantly promoted by fibroblasts derived from CXCL12. CXCL6 and CXCL2 could significantly enhance HUVEC proliferation and migration(P < 0.01). CXCL6 and CXCL2 enhanced angiogenesis by HUVECs when cultured with fibroblast cells and colon cancer cells(P < 0.01). CXCL12 also enhanced the invasion of colon cancer cells. Stromal cell-derived CXCL12 promoted the secretion level of CXCL6 and co-operatively promoted metastasis of colon carcinoma through activation of the PI3K/Akt/m TOR pathway.CONCLUSION Fibroblast-derived CXCL12 enhanced the CXCL6 secretion of colon cancer cells,and both CXCL12 and CXCL6 co-operatively regulated the metastasis via the PI3K/Akt/m TOR signaling pathway. Blocking this pathway may be a potential anti-metastatic therapeutic target for patients with colon cancer.
基金Supported by the Grant from National Center for Genetic Engineering and Biotechnology,Thailand and Rajavithi HospitalFund
文摘AIM:To evaluate the expression of C-X-C motif chemokine receptor 4(CXCR4)and its signaling cascades,which were previously identified as a key factor for cancer cell progression and metastasis,in cholangiocarcinoma cell lines.METHODS:The expression of CXCR4 and its signaling cascades were determined in the cholangiocarcinoma cell lines(RMCCA1 and KKU100)by Western blotting.The invasion assays and the detection of actin polymerization were tested in these cholangiocarcinoma cells treated with CXC chemokine ligand-12(CXCL12).RESULTS:Expression of CXCR4 was detected in both cholangiocarcinoma cell lines and activation of CXCR4 with CXCL12 triggered the signaling via the extracellular signal-regulated kinase-1/2(ERK1/2)and phosphoinositide 3-kinase(PI3K)and induction of cholangiocarcinoma cell invasion,and displayed high levels of actin polymerization.Addition of CXCR4 inhibitor(AMD3100)abrogated CXCL12-induced phosphorylation of MEK1/2 and Akt in these cells.Moreover,treatment with MEK1/2 inhibitor(U0126)or PI3K inhibitor(LY294 002)also attenuated the effect of CXCL12-induced cholangiocarcinoma cell invasion.CONCLUSION:These results indicated that the activation of CXCR4 and its signaling pathways(MEK1/2 and Akt)are essential for CXCL12-induced cholangiocarcinoma cell invasion.This rises Implications on a potential role for the inhibition of CXCR4 or its signal cascades in the treatment of cholangiocarcinoma.
文摘Objective The expression of CXCL12(stromal cell-derived factor-1)-CXCR4(chemokine receptors-4) in osteosarcoma and its role in angiogenesis were examined.Methods The expression of CXCR4 and CXCL12 in 40 cases of osteosarcoma was detected by immunohistochemistry and real-time fluorescence quantitative PCR.The expression of CD34 in osteosarcoma was detected by immunohistochemistry.Morphometric image analysis was performed to measure microvessel density(MVD).Additionally,the relationship between CXCL12 and CXCR4 expression and MVD of osteosarcoma and pulmonary metastasis were analyzed.Results The positive rates of CXCL12 and CXCR4 protein expression in osteosarcoma were 40.0%(16/40) and 60.0%(24/40),respectively.Fluorescence quantitative real-time PCR indicated that the expression level of CXCR4 m RNA in pulmonary metastatic osteosarcoma was higher than that in nonpulmonary metastatic osteosarcoma(P < 0.01).The level of MVD in pulmonary metastatic osteosarcoma was higher than that in non-pulmonary metastatic osteosarcoma(P < 0.01).Conclusion The expression level of CXCR4 was significantly associated with pulmonary metastasis and angiogenesis of osteosarcoma.
