Expression Of Stem Cell Marker CD133 Research Articles

Clinical significance of stem cell marker CD133 expression in colorectal cancer.

CD133, a glycoprotein, is expressed in different types of human stem cells and tumor cells. Detection of altered CD133 expression in colorectal cancer tissues could be useful as a marker for the prediction of colorectal tumorigenesis, progression, and prognosis. A total of 19 fresh and 145 paraffin-embedded tissue specimens from colorectal cancer patients were obtained for detection of CD133 expression using flow cytometry and immunohistochemistry, respectively. The tumorigenic capacity of tumor cells from 19 patients was assessed in nude mice. Association of CD133 expression was then analyzed for clinical significance. The percentage of CD133-positive (CD133⁺) tumor cell population ranged between 0.84% and16.75% (mean ratio =7.15%) of tumor cells in the 19 freshly isolated tissue samples. CD133 expression in tumor cells was associated with tumor lymph node metastasis (9.81% vs. 3.22%; p=0.013) and poor tumor differentiation (8.32% vs. 5.07%; p=0.043). In the 145 paraffin-embedded samples, CD133⁺ colorectal cancer was also associated with local recurrence of tumorigenesis (p=0.035) and distant metastasis (p=0.017), while patients with over 5% CD133+ tumor cells exhibited a decreased survival rate (p=0.001). Multivariate COX analysis showed that the depth of tumor invasion, histology, stagWaes, lymph node metastasis, and CD133 expression were all independent prognosis factors for colorectal cancer (p=0.032, 0.011, 0.001, 0.002, and 0.030, respectively). Furthermore, as few as 5,000 CD133⁺ colorectal cancer HCT116 cells were sufficient to form tumor xenografts, whereas 1x10⁵ CD133⁻ tumor cells failed to develop tumor xenografts in nude mice. CD133 expression is a useful biomarker for prediction of colorectal cancer progression and survival of patients.

Platinum sensitivity and CD133 expression as risk and prognostic predictors of central nervous system metastases in patients with epithelial ovarian cancer.

BackgroundTo characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC).MethodsA retrospective analysis of Xijing Hospital electronic medical records was conducted to identify patients with pathologically confirmed EOC and CNS metastases. In addition to patient demographics, tumor pathology, treatment regimens, and clinical outcomes, we compared putative cancer stem cell marker CD133 expression patterns in primary and metastatic lesions as well as in recurrent EOC with and without CNS metastases.ResultsAmong 1366 patients with EOC, metastatic CNS lesions were present in 29 (2.1%) cases. CD133 expression in primary tumor was the only independent risk factor for CNS metastases; whilst the extent of surgical resection of primary EOC and platinum resistance were two independent factors significantly associated with time to CNS metastases. Absence of CD133 expression in primary tumors was significantly associated with high platinum sensitivity in both patient groups with and without CNS metastases. Platinum resistance and CD133 cluster formation in CNS metastases were associated with decreased survival, while multimodal therapy including stereotactic radiosurgery (SRS) for CNS metastases was associated with increased survival following the diagnosis of CNS metastases.ConclusionsThese data suggest that there exist a positive association between CD133 expression in primary EOC, platinum resistance and the increased risk of CNS metastases, as well as a less favorable prognosis of EOC. The absence of CD133 clusters and use of multimodal therapy including SRS could improve the outcome of metastatic lesions. Further investigation is warranted to elucidate the true nature of the association between platinum sensitivity, CD133 expression, and the risk and prognosis of CNS metastases from EOC.

Correction: Prognostic Value of Cancer Stem Cell Marker CD133 Expression in Gastric Cancer: A Systematic Review

In the list of references, 29 is incorrect. Reference 29 should read, Coco C, Zannoni GF, Caredda E, Sioletic S, Boninsegna A, et al. (2012) Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients. J Exp Clin Cancer Res. 31: 71. Additionally, the affiliation for Dr. Xian-Ming Mo should be Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Prognostic Value of Cancer Stem Cell Marker CD133 Expression in Gastric Cancer: A Systematic Review

ObjectiveTo investigate the correlation between CD133-positive gastric cancer and clinicopathological features and its impact on survival.MethodsA search in the Medline and Chinese CNKI (up to 1 Dec 2011) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1 etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features.ResultsA total of 773 gastric cancer patients from 7 studies were included. The median rate of CD133 expression by immunohistochemistry (IHC) was 44.8% (15.2%–57.4%) from 5 studies, and that by reverse transcription polymerase chain reaction (RT-PCR) was 91.3% (66.7%–100%) from 4 studies. The accumulative 5-year overall survival rates of CD133-positive and CD133-negative patients were 21.4% and 55.7%, respectively. Meta-analysis showed that CD133-positive patients had a significant worse 5-year overall survival compared to the negative ones (OR = 0.20, 95% CI 0.14–0.29, P<0.00001). With respect to clinicopathological features, CD133 overexpression by IHC method was closely correlated with tumor size, N stage, lymphatic/vascular infiltration, as well as TNM stage.ConclusionCD133-positive gastric cancer patients had worse prognosis, and was associated with common clinicopathological poor prognostic factors.

Abstract 5362: Multidrug-resistance (MDR-1) gene expression in immature glioma cells

Abstract Cancer stem cell hypothesis suggests that small populations of stem-like cells exist in the tumor mass and harbor drug resistance and low radio-sensitivity, and thus resulting in tumor recurrence after various treatments. In this study, we investigated the relationship between cell differentiation and drug resistant gene expression in glioblastoma. Glioma stem-like cells freshly isolated from surgical specimens were enriched in tumor sphere (TS) culture and were more resistant to anti-cancer drugs compared with their differentiated cells in cell viability assay. These cells were also tested for phosphorylation of histone H2AX at Ser139, a biomarker of DNA lesions including DNA double-strand and single-strand breaks. Differentiated cells were much more susceptible to anti-cancer drug-induced DNA damage, compared with TS cells. The expression of drug resistance genes, MDR-1, MRP-1 and MRP-2 in TS cells was more than those in their differentiated cells by RT-PCR analysis. However, there was no correlation between drug resistance genes and stem cell marker CD133 expression. It is possibly caused by another cell population expressing drug resistance genes, therefore, we sought to define the existence of progenitor cells in glioma by detection of glial progenitor marker, A2B5 using flow cytometric analysis. CD133 and A2B5 positive cells were more abundant in TS cells and were decreased during induction of differentiation. The expression of MDR-1 was frequently observed in CD133+/A2B5−, CD133+/A2B5+ and CD133−/A2B5+ cells. Reduction of MDR-1 expression concomitantly occurred with the differentiation of these immature glioma cells. Thus, it is revealed that CD133 negative cells expressing MDR-1 are A2B5-positive glioma cells. These results suggest that drug resistance genes are expressed not only in tumor stem cells but also in progenitor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5362. doi:1538-7445.AM2012-5362

Characterization of a new human melanoma cell line with CD133 expression

A novel human malignant melanoma cell line, designated MEL-RC08, was established from a pericranial metastasis of a malignant melanoma of the skin. The cell line has been subcultured for more than 150 passages and is tumorigenic in nude mice. Growth kinetics, cytogenetics, flow cytometry, and molecular techniques for analysis of the genes implicated in cell cycle control; mutations in BRAF, NRAS, C-KiT, RB, and TP53 genes; and amplification of MDM2, CDK4, and cyclin D1 have been studied. Cytogenetically, the tumor and the cell line showed a hypertriploid karyotype with many clonal numeric and structural abnormalities. DNA flow cytometry showed an aneuploid peak with a DNA index value of 1.5. Mutations in TP53 and BRAF genes were demonstrated in both tumor and cell line. Furthermore, stem cell marker CD133 expression was detected in most cells, together with other stem cell markers, suggesting the presence of cells with tumor-initiating potential in this cell line.

Overexpression of Cell Cycle Progression Inhibitor Geminin is Associated with Tumor Stem-Like Phenotype of Triple-Negative Breast Cancer

PurposeTriple-negative breast cancer, has a significant clinical relevance being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. For this reason, identifying the molecular pathways associated with increased aggressiveness, for example the presence of stem cell populations within the tumor and alteration of genes associated with cell cycle regulation represents an important objective in the clinical research into this neoplasm.MethodsTo investigate the role of cell cycle progression inhibitor Geminin in triple-negative breast cancers and its potential correlation with stem-like phenotype of this neoplasm, we used tissue microarray technology to build a specific triple-negative breast cancer tissue micro-array. Geminin and cancer stem cell marker CD133 expression was further investigated at the mRNA level for selected breast tumor samples through realtime polymerase chain reaction quantification.ResultsOur results showed that CD133 expression was significantly associated to high Geminin expression (p=0.017), a strong association between Ki-67 and tumor grade (p=0.020) and an inverse association between Geminin expression and lymphonode metastases (p=0.058), and a trend of statistically significance between Geminin marker expression and survival of triple-negative breast cancer patients (p=0.076).ConclusionThe strong association between the expression of CD133 and Geminin could be useful in molecular stratification of breast tumors and in particular of triple-negative breast cancers.

Association of stem cell marker CD133 expression with dissemination of glioblastomas

Dissemination of glioblastoma was once considered rare but is now increasingly encountered with longer survival of glioblastoma patients. Despite the potential negative impact of dissemination on clinical outcome, however, molecular markers useful for prediction of dissemination risk still remains ill defined. We tested in this study for an association between the expression of stem cell marker CD133 and the risk of dissemination in 26 cases of glioblastoma (16 with dissemination and 10 without dissemination). The protein expression of CD133 was examined by western blot analysis of tumor specimens, and the CD133 expression levels were quantified by densitometry and normalized to beta-actin. The results indicated that CD133 expression levels are significantly higher in glioblastomas with dissemination (mean 10.3, range 0.20-27.8) than in those without (mean 1.18, range 0.07-3.58). The results suggest that CD133 could be a molecular predictor of glioblastoma dissemination, and also give rise to an intriguing idea that CD133-positive cancer stem cells may be implicated in the initiation of disseminated lesions.

Stem Cell Marker CD133 Expression Predicts Outcome in Glioma Patients

Evidence strongly indicates that a small fraction of cells within a tumor known as cancer stem cells (CSCs) drive tumorigenesis in solid neoplasms, including gliomas. CSCs are hypothesized not only to initiate new tumors but also to mediate recurrence by resistance to standard anticancer therapies. The CSC population has been enriched from brain and other tumors using the stem cell surface antigen CD133. CD133+ glioma cells are highly tumorigenic in animal models. For the first time, researchers at the German Cancer Research Center in Heidelberg, Germany recently showed that CD133 expression in primary tumor specimens correlates with survival and outcome measures in patients with gliomas (Clin Cancer Res 14:123–129, 2008). This group analyzed CD133 expression by immunohistochemistry in a series of surgical pathological specimens from 95 gliomas of various grades. CD133 expression and the topographical arrangement of CD133+ cells into clusters significantly increased with higher tumor grade. In 18 of 24 Grade II specimens, CD133 was either not detected or, when detected, was present in less than 1% of tumor cells. In contrast, CD133 was present in greater than 5% of tumor cells in 45 of 47 glioblastomas multiforme and present in 10 to 50% of these cells in 21 of those tumors. A high percentage of CD133+ tumor cells and the presence of clusters correlated with decreased progression-free and overall survival, independent of tumor grade, extent of surgical resection, or age. Moreover, tumor recurrence and progression from lower to higher grade were predicted by an increasing proportion of CD133+ cells within the initial specimen. CD133 was colocalized in a subset of nestin+ cells, indicating that CD133 expression may identify an increasingly tumorigenic subpopulation of CSCs. Further, CD133 was coexpressed with epidermal growth factor receptor vIII mutant, when present, proving that CD133+ cells derived from the tumor. This is one of a handful of recently published reports suggesting that a subset of cells within human gliomas express known neural stem cell markers (CD133, Sox2, Musashi-1, and others) and that such expression correlates with clinical outcomes. The CSC hypothesis dictates that targeting and eradicating these tumorigenic cells may significantly improve glioma treatment. Homing in on CSCs by these antigens may be confounded by their expression in normal neural stem cells, but work such as this may ultimately lead to better treatments and outcomes for patients.FIGURE: Differential expression of CD133 in gliomas of various grades correlates with clinical outcome. A, CD133 was not detectable in some World Health Organization (WHO) Grade II gliomas, whereas expression was detected in relatively few cells in other tumors of the same grade (B, arrows). C, WHO Grade III anaplastic astrocytoma with an increased percentage of CD133+ cells. D, WHO Grade IV glioblastoma multiforme with CD133+ cells arranged in clusters (arrowheads). E, Recurrence and malignant progression correlated with increased CD133 expression in WHO Grade II and III gliomas. F, Kaplan-Meier curves depict progression to glioblastoma multiforme and overall survival (G) in relation to higher CD133 expression in WHO Grade II gliomas. From Clin Cancer Res (14:123–129, 2008).BRIAN M. HOWARD, MD JOHN A. BOOCKVAR, MD STEM CELL RESEARCH

Endothelial progenitor marker CD133 mRNA expression in peripheral blood mononuclear cells predicts outcome of cancer patients

10087 Background: We examined whether expression of CD133, a surface molecule expressed on progenitors of hematopoietic and endothelial lineages, is increased in the peripheral blood mononuclear cells (PBMC’s) of cancer patients. Furthermore we correlated CD133 mRNA expression with tumor prognostication factors and overall survival. Methods: PBMC’s were isolated from the blood of 130 advanced cancer patients (43 renal cell carcinoma, 27 colorectal cancer, 34 prostate cancer, 27 head and neck cancer). Clinicopathological parameters were obtained. Median follow-up time was 16 months after inclusion (range 3–33 months). For the quantification of CD133 mRNA we used a real-time detection and quantification method based on nucleic acid sequence-based amplification (NASBA). Also U1A DNA was quantified as internal control for input and isolation. CD133 mRNA copy numbers were expressed as copies per 10.000 cells, as determined by U1A DNA. Results: Patients with metastasized disease have a significant increase in CD133 mRNA as compared to patients without metastasis. This increase is strongest in patients with bone metastasis. Subgroup analysis in patients with bone involvement show that CD133 mRNA also correlates with PSA (n=34)and inversely with hemoglobin (n=50). CD133 mRNA expression is an independent predictor for overall survival in Cox’s multivariate analysis (variables in the model included age, hemoglobin, metastasis, previous treatment and CD133 as categorical variable). A CD133 mRNA cut-off value was established by Receiver Operating Characteristic analysis of CD133 expression in relationship to survival (sensitivity 64% and specificity 71%). Cancer patients with more than 200 copies of CD133 mRNA, demonstrate a decreased survival compared to patients with lower CD133 expression (median survival 8 and 15.4 months, respectively). In patients with bone metastasis the median survival of high and low expressers is 6.3 months and 21.9 months, respectively. Conclusions: mRNA expression of stem-cell marker CD133 is increased in cancer patients with metastasized disease and an independent prognostic factor for overall survival. Increased CD133 mRNA expression may reflect an activated angiogenic state in these cancer patients. [Table: see text]