AIM： To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS： A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochem...AIM： To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS： A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS： Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 （55.6%） of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 （69.4%） of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes＇ stage and lymph node metastasis. Nuclear staining was also observed in 24 （19.4%） of 124 samples and closely associated with Dukes＇ stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION： Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.展开更多
AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pan...AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer. METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed. RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues (P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4-and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis (P = 0.001), S100A4-(P = 0.008) and VEGF-positive expression (P = 0.016) were significantly independent prognostic predictors (P < 0.05). CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.展开更多
AIM： To investigate a potential role of S100A4 in esoph- agus squamous cell carcinoma metastasis （ESCCs）.METHODS： Expression of $100A4 and E-cadherin were analyzed in frozen sections from ESCCs （metastasis, n = 2...AIM： To investigate a potential role of S100A4 in esoph- agus squamous cell carcinoma metastasis （ESCCs）.METHODS： Expression of $100A4 and E-cadherin were analyzed in frozen sections from ESCCs （metastasis, n = 28; non-metastasis, n = 20） by reverse transcrip- tion-polymerase chain reaction, quantitative polymerase chain reaction and immunohistochemistry. To explore the influence of $100A4 on esophageal cancer invasion and metastasis, $100A4 was overexpressed or silenced by $100A4 siRNA in TE-13 or Eca-109 cells/n vitro and /n vivo.展开更多
Objective Pancreatic cancer is one of the most deadly cancers, which is characterized by its high metastatic potential. S100A4 is a major prometastatic protein involved in tumor invasion and metastasis which precise r...Objective Pancreatic cancer is one of the most deadly cancers, which is characterized by its high metastatic potential. S100A4 is a major prometastatic protein involved in tumor invasion and metastasis which precise role in pancreatic cancer has not been fully investigated. We knocked down the S100A4 gene in the Bxpc-3 pancreatic cancer cell line via RNA interference to study the changes in cell behavior. Methods Real-time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels of S100A4, matrix metalloproteinase （MMP）-2, E-cadherin and thrombospondin （TSP）-I. Transwell chambers were used to detect the migration and invasion abilities; a cell adhesion assay was used to detect adhesion ability; colony forming efficiency was used to detect cell proliferation; flow cytometry was used to detect apoptosis. Results S100A4 mRNA expression was reduced to 17% after transfection with SIOOA4-siRNA, and protein expression had a similar trend, mRNA and protein expression of MMP-2 was reduced and that of E-cadherin and TSP-1 was elevated, indicating that S100A4 affects their expression. S100A4-silenced cells exhibited a marked decrease in migration and invasiveness and increased adhesion, whereas overall proliferation and apoptosis were not overtly altered. Conclusion S100A4 and its downstream factors play important roles in pancreatic cancer invasion, and silencing AIOOA4 can significantly contain the invasiveness of pancreatic cancer.展开更多
Intercellular cross-talk plays important roles in cancer progression and metastasis.Yet how these cancer cells interact with each other is still largely unknown.Exosomes released by tumor cells have been proved to be ...Intercellular cross-talk plays important roles in cancer progression and metastasis.Yet how these cancer cells interact with each other is still largely unknown.Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators.We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma(HCC).Exosomes were extracted from HCC cells of different metastatic potentials.The metastatic effects of exosomes derived from highly metastatic HCC cells(HMH)were evaluated both in vitro and in vivo.Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines,xenograft tumor samples,and functional analyses.Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells(LMH).S100 calcium-binding protein A4(S100A4)was identified as a functional factor in exosomes derived from HMH.S100A4r,ch exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4^(rich) exosomes or controls.Moreover,exosomal S100A4 could induce expression of osteopontin(OPN),along with other tumor metastasis/stemness-related genes.Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation.HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis.In conclusion,exosomes from HMH could promote the metastatic potential of LMH,and exosomal S100A4 is a key enhancer for HCC metastasis,activating STAT3 phosphorylation and up-regulating OPN expression.This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.展开更多
基金Supported by the Korea Science and Engineering Foundation, No.R13-2002-005-01004-0
文摘AIM： To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS： A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS： Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 （55.6%） of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 （69.4%） of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes＇ stage and lymph node metastasis. Nuclear staining was also observed in 24 （19.4%） of 124 samples and closely associated with Dukes＇ stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION： Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.
文摘AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer. METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed. RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues (P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4-and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis (P = 0.001), S100A4-(P = 0.008) and VEGF-positive expression (P = 0.016) were significantly independent prognostic predictors (P < 0.05). CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.
文摘AIM： To investigate a potential role of S100A4 in esoph- agus squamous cell carcinoma metastasis （ESCCs）.METHODS： Expression of $100A4 and E-cadherin were analyzed in frozen sections from ESCCs （metastasis, n = 28; non-metastasis, n = 20） by reverse transcrip- tion-polymerase chain reaction, quantitative polymerase chain reaction and immunohistochemistry. To explore the influence of $100A4 on esophageal cancer invasion and metastasis, $100A4 was overexpressed or silenced by $100A4 siRNA in TE-13 or Eca-109 cells/n vitro and /n vivo.
文摘Objective Pancreatic cancer is one of the most deadly cancers, which is characterized by its high metastatic potential. S100A4 is a major prometastatic protein involved in tumor invasion and metastasis which precise role in pancreatic cancer has not been fully investigated. We knocked down the S100A4 gene in the Bxpc-3 pancreatic cancer cell line via RNA interference to study the changes in cell behavior. Methods Real-time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels of S100A4, matrix metalloproteinase （MMP）-2, E-cadherin and thrombospondin （TSP）-I. Transwell chambers were used to detect the migration and invasion abilities; a cell adhesion assay was used to detect adhesion ability; colony forming efficiency was used to detect cell proliferation; flow cytometry was used to detect apoptosis. Results S100A4 mRNA expression was reduced to 17% after transfection with SIOOA4-siRNA, and protein expression had a similar trend, mRNA and protein expression of MMP-2 was reduced and that of E-cadherin and TSP-1 was elevated, indicating that S100A4 affects their expression. S100A4-silenced cells exhibited a marked decrease in migration and invasiveness and increased adhesion, whereas overall proliferation and apoptosis were not overtly altered. Conclusion S100A4 and its downstream factors play important roles in pancreatic cancer invasion, and silencing AIOOA4 can significantly contain the invasiveness of pancreatic cancer.
基金supported by the Program of Shanghai Academic Research Leader(20XD1400900)the National Key Research and Development Program of China(2017YFC1308604)the National Natural Science Foundation of China(81702857,81672820,81930074,91959203 and 81372647).
文摘Intercellular cross-talk plays important roles in cancer progression and metastasis.Yet how these cancer cells interact with each other is still largely unknown.Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators.We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma(HCC).Exosomes were extracted from HCC cells of different metastatic potentials.The metastatic effects of exosomes derived from highly metastatic HCC cells(HMH)were evaluated both in vitro and in vivo.Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines,xenograft tumor samples,and functional analyses.Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells(LMH).S100 calcium-binding protein A4(S100A4)was identified as a functional factor in exosomes derived from HMH.S100A4r,ch exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4^(rich) exosomes or controls.Moreover,exosomal S100A4 could induce expression of osteopontin(OPN),along with other tumor metastasis/stemness-related genes.Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation.HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis.In conclusion,exosomes from HMH could promote the metastatic potential of LMH,and exosomal S100A4 is a key enhancer for HCC metastasis,activating STAT3 phosphorylation and up-regulating OPN expression.This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.
