Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituit...Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma (21 invasive and 14 non-invasive) patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. Results Flow cytometric analyses showed that the percentage of CXCR4- and CXCL12-positive cells from invasive pituitary adenomas (IPA) was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas (nlPA) (P〈O.05). Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas (P〈O.05). In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. Conclusion Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.展开更多
Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whethe...Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound(AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.Methods Wst-1 assays were used to confirm the effect of novel compounds on proliferation.Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.Results There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.Conclusion Our results have clarified the tumor specificity of CD147 and its drug target characteristics.The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.展开更多
The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievem...The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved (including an estimate of the number of leucocyte surface molecules still to be discovered), and how the field can best move forward.展开更多
AIM:To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC). METHODS:Twenty-two ...AIM:To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC). METHODS:Twenty-two patients (15 men and 7 women; median age 68 years,range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC. Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition,the degree of staining within tumor tissue was compared according to a number of clinicopathological variables. RESULTS:The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues,even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP.展开更多
Objective: The aim of this study was to investigate the expressions of CD147 and CK19 in hepatocellular car- cinoma (HCC) and their clinical significance. Methods: The expressions of CD147 and CK19 were determined by ...Objective: The aim of this study was to investigate the expressions of CD147 and CK19 in hepatocellular car- cinoma (HCC) and their clinical significance. Methods: The expressions of CD147 and CK19 were determined by tissue microarray and immunohistochemistry (IHC) in 272 cases of HCC and 81 cases of adjacent tumorous tissue. Results: The positive expression of CD147 in HCC and adjacent tumorous tissue was 73.53% (200/272) and 13.58% (11/81) with signifi- cant difference (P < 0.05). The positive expression of CK19 in HCC and adjacent tumorous tissue was 14.34% (39/272) and 0 (0/81) with significant difference (P < 0.05). The positive expression of CD147 were closely correlated to the histological grade, clinical stage, tumor-free survival, diameter of tumor and embolus of cancer in aqueduct or portal vein; but not to the patients' sex, age, liver cirrhosis, AFP level, infection of HBV, lymph node metastasis, number of tumor, invasion liver involucrum and the micro-satellites (P > 0.05). The expression of CK19 in HCC were closely correlate to the tumor-free survival, histological grade, diameter of tumor, liver cirrhosis, micro-satellites, lymph node metastasis and clinical stage; but not to patients' sex, age, number of tumor, invasion liver involucrum, AFP level, infection of HBV and embolus of cancer in aqueduct or portal vein (P > 0.05). Among the patients of positive expression of CD147, the median replacing time and overall survival were 13 and 24 months, lower than 48 and 60 months in the patients of negative expression (P < 0.05). Among the patients of positive expression of CK19, the median replacing time and overall survival were 7 and 13 months, lower than 31 and 42 months in the patients of negative expression (P < 0.05). The expression of CD147 had no correlation with the expression of CK19 (r = 0.061, P = 0.317). Conclusion: The positive of CD147 and CK19 closely correlate with the clinical prognosis of HCC, it may indicate poor prognosis of HCC.展开更多
Objective: To investigate the expression of CD147 on human ovarian neoplasm cell lines and its influence on production and activation of matrix metallproteinases(MMPs). Methods: The expression of CD147 on different hu...Objective: To investigate the expression of CD147 on human ovarian neoplasm cell lines and its influence on production and activation of matrix metallproteinases(MMPs). Methods: The expression of CD147 on different human ovarian neoplasm cell lines was studied by western blotting. Co-culture was carried out to investigate the stimulative effect of the positive expression CD147 cell HO-8910 on the production of MMPs of fibroblast cell in vitro. Zymography and immune blotting were used to study the production and activity of positive MMPs, at the time, to explore the relation between CD147 and MMPs. Results: CD147 was positively presented in 2 ovarian neoplasm cell lines(HO-8910,3-AO), but in SKOV3, TC-1,NIN3T3 cell was negative. MMP-2 and MMP-9 were detected by HO-8910 cell line, mouse fibroblast cell and co-culture cells; but the expression in co-culture cell is obviously higher than individual cultures of each type alone.CD147 stimulated MMPs in dose-dependent manner. Conclusion: CD147 causes increased production and activation of MMP-2, MMP-9.CD147 is probably a indirect marker of some ovarian cancer cells with invasion and metastasis.展开更多
Objective: The aim of this study was to investigate the expression of CD147 and matrix metalioprpteinsae 9 (MMP-9) in children with non-Hodgkin's lymphoma (NHL) and the relations between expressions of CD147 & ...Objective: The aim of this study was to investigate the expression of CD147 and matrix metalioprpteinsae 9 (MMP-9) in children with non-Hodgkin's lymphoma (NHL) and the relations between expressions of CD147 & MMP-9 and the clinical indexes. Methods: Specimens excised from NHL patients were prepared. Expression of CD147 and MMP-9 were tested by SABC immunohistochemistry and its correlation to clinical results were analyzed in this report. Results: The positive rate of CD147 expression was 73% (45/62), and that of MMP-9 expression was 81% (50/62). There was a positive correlation between CD147 and MMP-9 expressions. CD147 expression intensity was linked to clinical myelo-infiltration, tumor size, LDH value, and clinical staging (P 〈 0.05), rather than children age, gender, or immune typing (P 〉 0.05); MMP-9 expression intensity was linked to myelo-infiltration, and clinical staging (P 〈 0.05), rather than age, gender, immune typing, tumor size, or LDH value (P 〉 0.05). Five-year survival rates were 78% (22/28) and 45% (15/34) in CD147 (-)-(+) and (++)-(+++) cases respectively, and those were 84% (21/25) and 43% (16/37) in MMP-9 (-)-(+) and (++)-(+++) cases respectively, the difference was significant. Conclusion: The elevated expression of CD147 and/or MMP-9 correlates with a poor clinical outcome in patients with NHL.展开更多
Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and ...Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.展开更多
基金supported by the key program for clinical research foundation of PUMC Hospital(Grant No.200611)
文摘Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma (21 invasive and 14 non-invasive) patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. Results Flow cytometric analyses showed that the percentage of CXCR4- and CXCL12-positive cells from invasive pituitary adenomas (IPA) was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas (nlPA) (P〈O.05). Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas (P〈O.05). In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. Conclusion Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.
基金supported by grants from the National Natural Science Foundation of China [grant number 81703003,Z.G.Fu and grant number 81700968,P.X]a China Postdoctoral Science Foundation Funded Project [Project No.:2017M623395 and Project No.:2018T111143]
文摘Objective Cancer is a serious threat to human health. Despite extensive research on cancer treatment,there is a growing demand for new therapies. CD147 is widely involved in tumor development, but it is unclear whether cancer cell malignancy is affected by CD147 expression level. The first compound(AC-73) targeting CD147 could only act on advanced tumors and inhibit metastasis. Therefore, new compounds with better anticancer activity should be explored.Methods Wst-1 assays were used to confirm the effect of novel compounds on proliferation.Apoptosis tests were used to evaluate their proapoptotic capacity. A nude mouse model was used to demonstrate in vivo anticancer activity and safety of the compounds. Western blots were used to suggest a molecule mechanism.Results There is a positive correlation between CD147 expression and tumor cell proliferation. A new compound, HA-08, was synthesized and proved to be more active than AC-73. HA-08 could inhibit cancer cell viability and promote cancer cell apoptosis both in vitro and in vivo. HA-08 induces cancer apoptosis, mainly by disrupting the CD147-CD44 interaction and then down-regulating the JAK/STAT3/Bcl-2 signaling pathway.Conclusion Our results have clarified the tumor specificity of CD147 and its drug target characteristics.The biological profile of HA-08 suggests that this compound could be developed as a potential anticancer agent.
文摘The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved (including an estimate of the number of leucocyte surface molecules still to be discovered), and how the field can best move forward.
文摘AIM:To make clear whether CD147 (EMMPRIN) expression in pathological tumor samples with a fine-needle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC). METHODS:Twenty-two patients (15 men and 7 women; median age 68 years,range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC. Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition,the degree of staining within tumor tissue was compared according to a number of clinicopathological variables. RESULTS:The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues,even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP.
文摘Objective: The aim of this study was to investigate the expressions of CD147 and CK19 in hepatocellular car- cinoma (HCC) and their clinical significance. Methods: The expressions of CD147 and CK19 were determined by tissue microarray and immunohistochemistry (IHC) in 272 cases of HCC and 81 cases of adjacent tumorous tissue. Results: The positive expression of CD147 in HCC and adjacent tumorous tissue was 73.53% (200/272) and 13.58% (11/81) with signifi- cant difference (P < 0.05). The positive expression of CK19 in HCC and adjacent tumorous tissue was 14.34% (39/272) and 0 (0/81) with significant difference (P < 0.05). The positive expression of CD147 were closely correlated to the histological grade, clinical stage, tumor-free survival, diameter of tumor and embolus of cancer in aqueduct or portal vein; but not to the patients' sex, age, liver cirrhosis, AFP level, infection of HBV, lymph node metastasis, number of tumor, invasion liver involucrum and the micro-satellites (P > 0.05). The expression of CK19 in HCC were closely correlate to the tumor-free survival, histological grade, diameter of tumor, liver cirrhosis, micro-satellites, lymph node metastasis and clinical stage; but not to patients' sex, age, number of tumor, invasion liver involucrum, AFP level, infection of HBV and embolus of cancer in aqueduct or portal vein (P > 0.05). Among the patients of positive expression of CD147, the median replacing time and overall survival were 13 and 24 months, lower than 48 and 60 months in the patients of negative expression (P < 0.05). Among the patients of positive expression of CK19, the median replacing time and overall survival were 7 and 13 months, lower than 31 and 42 months in the patients of negative expression (P < 0.05). The expression of CD147 had no correlation with the expression of CK19 (r = 0.061, P = 0.317). Conclusion: The positive of CD147 and CK19 closely correlate with the clinical prognosis of HCC, it may indicate poor prognosis of HCC.
文摘Objective: To investigate the expression of CD147 on human ovarian neoplasm cell lines and its influence on production and activation of matrix metallproteinases(MMPs). Methods: The expression of CD147 on different human ovarian neoplasm cell lines was studied by western blotting. Co-culture was carried out to investigate the stimulative effect of the positive expression CD147 cell HO-8910 on the production of MMPs of fibroblast cell in vitro. Zymography and immune blotting were used to study the production and activity of positive MMPs, at the time, to explore the relation between CD147 and MMPs. Results: CD147 was positively presented in 2 ovarian neoplasm cell lines(HO-8910,3-AO), but in SKOV3, TC-1,NIN3T3 cell was negative. MMP-2 and MMP-9 were detected by HO-8910 cell line, mouse fibroblast cell and co-culture cells; but the expression in co-culture cell is obviously higher than individual cultures of each type alone.CD147 stimulated MMPs in dose-dependent manner. Conclusion: CD147 causes increased production and activation of MMP-2, MMP-9.CD147 is probably a indirect marker of some ovarian cancer cells with invasion and metastasis.
文摘Objective: The aim of this study was to investigate the expression of CD147 and matrix metalioprpteinsae 9 (MMP-9) in children with non-Hodgkin's lymphoma (NHL) and the relations between expressions of CD147 & MMP-9 and the clinical indexes. Methods: Specimens excised from NHL patients were prepared. Expression of CD147 and MMP-9 were tested by SABC immunohistochemistry and its correlation to clinical results were analyzed in this report. Results: The positive rate of CD147 expression was 73% (45/62), and that of MMP-9 expression was 81% (50/62). There was a positive correlation between CD147 and MMP-9 expressions. CD147 expression intensity was linked to clinical myelo-infiltration, tumor size, LDH value, and clinical staging (P 〈 0.05), rather than children age, gender, or immune typing (P 〉 0.05); MMP-9 expression intensity was linked to myelo-infiltration, and clinical staging (P 〈 0.05), rather than age, gender, immune typing, tumor size, or LDH value (P 〉 0.05). Five-year survival rates were 78% (22/28) and 45% (15/34) in CD147 (-)-(+) and (++)-(+++) cases respectively, and those were 84% (21/25) and 43% (16/37) in MMP-9 (-)-(+) and (++)-(+++) cases respectively, the difference was significant. Conclusion: The elevated expression of CD147 and/or MMP-9 correlates with a poor clinical outcome in patients with NHL.
基金supported by the Science and Technology Project of Shaanxi Province,China(No.2021 PT-047,2022 PT-43,2022JQ-874)the Young Elite Scientist Sponsorship Program by Cast(China Association for Science andTechnology)(No.2020QNRC001).
文摘Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.