CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

Are stem cell marker expression and cd133 analysis relevant to differentiate colorectal cancer? / A expressão de marcadores de células-tronco e a análise do cd133 são relevantes na diferenciação do câncer colorretal?

ABSTRACT Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

RESUMO Racional: CD133 e AXL são descritos na literatura como marcadores de células-tronco tumorais, e c-MYC cumpre papel chave como mecanismo de regulação celular no câncer colorretal (CCR). Objetivo: Avaliar o papel prognóstico dos biomarcadores CD133, AXL e c-MYC e sua associação com características clinicopatológicas de adenocarcinomas e adenomas colorretais. Métodos: Um total de 156 pacientes com adenocarcinomas de estádio UICC I-IV (n=122) e adenomas (n=34) colorretais foram avaliados. Microarranjos teciduais (TMA) dos tumores primários e adenomas foram realizados em busca de expressão de CD133, c-MYC e AXL, com posterior análise de relação significativa com características clinicopatológicas. Resultados: Adenocarcinomas pobremente diferenciados e progressão de doença foram fatores de risco independentes para má sobrevida global. A taxa mediana de sobrevida global foi de 30 meses. Expressão positiva de CD133 (35,9% dos casos), particularmente em cânceres de cólon direito (44,8% dos casos CD133+), correlacionou-se negativamente com óbito na análise univariada, sem significância estatística na análise multivariada. c-MYC (15,4% dos casos) teve predomínio de expressão em pacientes com estádio avançado com metástases distantes (não-pulmonares/não-hepáticas). Expressão de AXL foi pouco encontrada, com predomínio em adenomas, com menor penetrância em displasia de alto grau. Conclusão: Expressão de CD133 não se associou com sobrevida global inferior em CCR. Enquanto AXL demonstrou resultados inconclusivos, expressão de c-MYC em tumores primários se associou-se à metástases à distância.

Are stem cell marker expression and cd133 analysis relevant to differentiate colorectal cancer? / A expressão de marcadores de células-tronco e a análise do cd133 são relevantes na diferenciação do câncer colorretal?

ABSTRACT Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

RESUMO Racional: CD133 e AXL são descritos na literatura como marcadores de células-tronco tumorais, e c-MYC cumpre papel chave como mecanismo de regulação celular no câncer colorretal (CCR). Objetivo: Avaliar o papel prognóstico dos biomarcadores CD133, AXL e c-MYC e sua associação com características clinicopatológicas de adenocarcinomas e adenomas colorretais. Métodos: Um total de 156 pacientes com adenocarcinomas de estádio UICC I-IV (n=122) e adenomas (n=34) colorretais foram avaliados. Microarranjos teciduais (TMA) dos tumores primários e adenomas foram realizados em busca de expressão de CD133, c-MYC e AXL, com posterior análise de relação significativa com características clinicopatológicas. Resultados: Adenocarcinomas pobremente diferenciados e progressão de doença foram fatores de risco independentes para má sobrevida global. A taxa mediana de sobrevida global foi de 30 meses. Expressão positiva de CD133 (35,9% dos casos), particularmente em cânceres de cólon direito (44,8% dos casos CD133+), correlacionou-se negativamente com óbito na análise univariada, sem significância estatística na análise multivariada. c-MYC (15,4% dos casos) teve predomínio de expressão em pacientes com estádio avançado com metástases distantes (não-pulmonares/não-hepáticas). Expressão de AXL foi pouco encontrada, com predomínio em adenomas, com menor penetrância em displasia de alto grau. Conclusão: Expressão de CD133 não se associou com sobrevida global inferior em CCR. Enquanto AXL demonstrou resultados inconclusivos, expressão de c-MYC em tumores primários se associou-se à metástases à distância.

Research progresses of CD133 in thyroid carcinoma / 中华核医学与分子影像杂志

CD133 has been confirmed as a stem cell surface marker in a variety of tumors.Specific markers of cancer stem cells in the thyroid cancer are not yet clear.Results of some studies showed that expression of CD133 was found in undifferentiated thyroid cancer cells which had the characteristics of stem cells.Those cells had the ability to self-renewal,multi-directional differentiation,potential development to cancer,and radio-and chemotherapy resistance.This article mainly views the progresses of CD133 in thyroid cancer research.

Expression of AC133 and EpCAM in human pulmonary adenocarcinoma and isolation of their double positive cells / 第二军医大学学报

Objective: To determine the expression of AC133 and EpCAM in human pulmonary adenocarcinoma by dual immunofluorescent labeling technique and to isolate AC133+ EpCAM+ cells by flow cytometry, so as to provide a basis for further investigation of human pulmonary adenocarcinoma stem cells. Methods: The human lung adenocarcinoma tissues were obtained and subjected to cryosection and dual immunofluorescent staining. AC133+ EpCAM+ cells in human pulmonary adenocarcinoma were identified by using laser confocal microscopy. The fresh adenocarcinoma tissues were prepared into single cell suspension with the collagen and red blood cell removed. AC133 and EpCAM were used to label cells and the AC133+ EpCAM+ cells were isolated by flow cytometry. ResuIts:AC133+ EpCAM + cells were found in human pulmonary adenocarcinoma and they could be isolated by flow cytometry. Conclusion:The existence of AC133+ EpCAM+ cells has been confirmed in the lung adenocarcinoma tissues; the double positive cells can be isolated by flow cytometry, which provides a basis for further investigation of lung cancer stem cells.

Effects of SDF-1 on the chemotaxis of cord blood AC133+ cells / 白血病·淋巴瘤

Objective To explore the effects of the stromal cell-derived factor on chemotaxis of cord blood ACl33+ cells.Methods The optimal SDF-1 concentration is detected in Transwell system.Migration was calculated from the number of cells found to have passed through an 8-um pore size polycarbonate membrane.Results The chemotactic rate of fresh cord blood AC133+ cells increases along with the concentration of SDF-1,however,it tends to be stable when the concentration of SDF-1 reaches 150 ng/ml.There is no difference in the chemotactic rate of cord blood AC133+ cells between the group with CXCR4-blocking antibody and the group without SDF-1.Conclusion Transwell Plate can simulate the phenomenon of cell crossing endothelium.The chemotactic rate of cord blood AC133+ cells increases progressively along with the concentration of SDF-1,however,the chemotactic rate tends to equability when SDF-1 reaches a certain concentration.The chemotactic rate does not have a marked change while continuing to increase the concentration of SDF-1.There is no difference in the chemotactic rate of cord blood AC133+ cells between the group using CXCR4-blocking antibody and the group without SDF-1.

Biological Characteristics of AC133 Antigen-Positive Acute Leukemia / 대한혈액학회지

BACKGROUND: AC133 antigen is a cell surface antigen which is selectively expressed on hematopoietic stem and progenitor cells. It has been reported that AC133 antigen is expressed on the subsets of CD34+ acute leukemia, and occasionally on CD34- acute leukemia. We investigated the clinical and biological characteristics of AC133 antigen-positive acute leukemia. METHODS: Thirty-six adult acute leukemia patients were analyzed using a cut-off criterion of 20% or more gated leukemic blasts expressing the AC133 antigen for AC133+ leukemia. The biological characteristics focused on apoptosis were examined using multicolor flow cytometry and Western blot analysis. RESULTS: AC133 antigen was expressed in 12 cases (33.3%). Eleven of 21 (52.4%) acute myelogenous leukemia (AML) patients and 1 of 15 (6.7%) acute lymphoblastic leukemia patients were positive for AC133 antigen, and the difference was significant. None of the clinical prognostic markers were significantly different between AC133+ and AC133- AML. Median disease free and overall survival time were not significantly different between AC133+ and AC133- AML. The expression rate of CD34 was significantly higher in AC133+ AML patients compared to those of AC133- AML (P=0.045). Among the apoptosis-related proteins, the Fas expression on the leukemic blasts was higher in the AC133+ AML (P=0.048), but Fas ligand, Bcl-2, caspase-3 expression rates were not significantly different between AC133+ and AC133- AML. The apoptosis rate was significantly lower in the Ara-C treated AC133+ AML (P=0.049), but the apoptosis rates to other apoptosis-inducing agents (doxorubicin, TNF-alpha) were not different between AC133+ and AC133- AML cells. We thought that there were some associations between a trend toward higher caspase-3 expression rates and lower Ara-C induced apoptosis rates in the AC133+ AML. CONCLUSION: There was no significant correlation between AC133 antigen expression and various clinical characteristics of acute leukemia, but the AC133 antigen might provide different biological characteristics including apoptosis from other immature cell surface markers. However, to verify the prognostic usefulness of AC133 antigen and the basis of the biological characteristics of AC133 antigen-positive acute leukemia, further study is needed.