AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in...AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.展开更多
AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed e...AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence ofCXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.展开更多
To review the implication of CXCR4 for gastrointestinal cancer, a ＂Pubmed＂ analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were ...To review the implication of CXCR4 for gastrointestinal cancer, a ＂Pubmed＂ analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were ＂cancer, malignoma, esophageal, gastric, colon, colorectal, hepatic, pancreatic, CXCR4, SDF- 1α, and SDF-1β＂. CXCR4 expression correlated with dissemination of diverse gastrointestinal malignomas. The CXCR4 ligand SDF-1α might act as ＂chemorepellent＂ while SDF-1β might act as ＂chemorepellent＂ for CTLs, inducing tumor rejection. The paracrine expression of SDF-1α was furthermore closely associated with neoangiogenesis. CXCR4 and its ligands influence the dissemination, immune rejection, and neoangiogenesis of human gastrointestinal cancers. Inhibition of CXCR4 might be an interesting therapeutic option.展开更多
Stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4(CXCR4)have been implicated in breast cancer metastasis.A significant association between HER2 and CXCR4 expression has been observed in human bre...Stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4(CXCR4)have been implicated in breast cancer metastasis.A significant association between HER2 and CXCR4 expression has been observed in human breast tumor tissues,and overexpression of CXCR4 is essential for HER2-mediated tumor metastasis.Moreover,CXCR4 expression is low in normal breast tissues and high in malignant tumors,suggesting that a blockade of CXCR4 may limit tumor metastasis.The present study investigated the action of a synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein Ⅱ against CXCR4(NT21MP)in inhibiting metastasis in vitro and in vivo.The results showed that chemotaxis of SKBR3 cells toward SDF-1αwas reduced by NT21MP in a dose-dependent manner(P<0.05).NT21MP inhibited tumor growth at 500μg/kg and in combination with Herceptin,the anti-HER2 antibody.The in vivo metastatic assay showed that NT21MP significantly inhibited pulmonary metastasis,and the number of metastatic tumor nodes on the surface of the lung was greatly decreased.Compared with the saline-treated control group,PCNA expression was dose-dependently decreased by NT21MP,the percentage of apoptotic cells was increased,and CXCR4 mRNA and protein expression were downregulated.In conclusion,NT21MP inhibits cellular proliferation,promotes apoptosis by downregulating CXCR4 expression,and suppresses the progression of primary and metastatic tumors.CXCR4 may be a useful therapeutic target for breast cancer,and NT21MP may serve as a potential target drug for the treatment of breast cancer metastasis.展开更多
基金Supported by The National Natural Science Foundation of China, No. 30772542
文摘AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.
基金Supported by grants from the Medical Research Fund of Hyogo Medical Association
文摘AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence ofCXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.
文摘To review the implication of CXCR4 for gastrointestinal cancer, a ＂Pubmed＂ analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were ＂cancer, malignoma, esophageal, gastric, colon, colorectal, hepatic, pancreatic, CXCR4, SDF- 1α, and SDF-1β＂. CXCR4 expression correlated with dissemination of diverse gastrointestinal malignomas. The CXCR4 ligand SDF-1α might act as ＂chemorepellent＂ while SDF-1β might act as ＂chemorepellent＂ for CTLs, inducing tumor rejection. The paracrine expression of SDF-1α was furthermore closely associated with neoangiogenesis. CXCR4 and its ligands influence the dissemination, immune rejection, and neoangiogenesis of human gastrointestinal cancers. Inhibition of CXCR4 might be an interesting therapeutic option.
基金supported by the Natural Science Foundation of Anhui Province(070413119)and Clinical Testing and Diagnose Key Disciplines of Anhui Province
文摘Stromal cell-derived factor-1 and its receptor CXC chemokine receptor-4(CXCR4)have been implicated in breast cancer metastasis.A significant association between HER2 and CXCR4 expression has been observed in human breast tumor tissues,and overexpression of CXCR4 is essential for HER2-mediated tumor metastasis.Moreover,CXCR4 expression is low in normal breast tissues and high in malignant tumors,suggesting that a blockade of CXCR4 may limit tumor metastasis.The present study investigated the action of a synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein Ⅱ against CXCR4(NT21MP)in inhibiting metastasis in vitro and in vivo.The results showed that chemotaxis of SKBR3 cells toward SDF-1αwas reduced by NT21MP in a dose-dependent manner(P<0.05).NT21MP inhibited tumor growth at 500μg/kg and in combination with Herceptin,the anti-HER2 antibody.The in vivo metastatic assay showed that NT21MP significantly inhibited pulmonary metastasis,and the number of metastatic tumor nodes on the surface of the lung was greatly decreased.Compared with the saline-treated control group,PCNA expression was dose-dependently decreased by NT21MP,the percentage of apoptotic cells was increased,and CXCR4 mRNA and protein expression were downregulated.In conclusion,NT21MP inhibits cellular proliferation,promotes apoptosis by downregulating CXCR4 expression,and suppresses the progression of primary and metastatic tumors.CXCR4 may be a useful therapeutic target for breast cancer,and NT21MP may serve as a potential target drug for the treatment of breast cancer metastasis.
