Expression Levels Of CD44v6 Research Articles

Inflammation-Related DNA Damage and Cancer Stem Cell Markers in Nasopharyngeal Carcinoma.

Nitrative and oxidative DNA damage plays an important role in inflammation-related carcinogenesis. To investigate the involvement of stem cells in Epstein-Barr virus infection-related nasopharyngeal carcinoma (NPC), we used double immunofluorescence staining to examine several cancer stem/progenitor cell markers (CD44v6, CD24, and ALDH1A1) in NPC tissues and NPC cell lines. We also measured 8-nitroguanine formation as an indicator of inflammation-related DNA lesions. The staining intensity of 8-nitroguanine was significantly higher in cancer cells and inflammatory cells in the stroma of NPC tissues than in chronic nasopharyngitis tissues. Expression levels of CD44v6 and ALDH1A1 were significantly increased in cancer cells of primary NPC specimens in comparison to chronic nasopharyngitis tissues. Similarly, more intense staining of CD44v6 and ALDH1A1 was detected in an NPC cell line than in an immortalized nasopharyngeal epithelial cell line. In the case of CD24 staining, there was no significant difference between NPC and chronic nasopharyngitis tissues. 8-Nitroguanine was detected in both CD44v6- and ALDH1A1-positive stem cells in NPC tissues. In conclusion, CD44v6 and ALDH1A1 are candidate stem cell markers for NPC, and the increased formation of DNA lesions by inflammation may result in the mutation of stem cells, leading to tumor development in NPC.

PP25 - Inflammation-related DNA damage in relation to the expression of cancer stemness markers in human nasopharyngeal carcinoma

Reactive nitrogen species are considered to participate in inflammation-related carcinogenesis through DNA damage. 8-Nitroguanine is a specific marker of inflammation-related carcinogenesis. Epstein-Barr virus infection-related nasopharyngeal carcinoma (NPC) is one of the most prevalent malignant tumors in southern China and Southeast Asia, and its prognosis has been poor for decades. Previously, we demonstrated that nitrative DNA damage, such as 8-nitroguanine formation, occurs in cancer cells of NPC patients (Ma et al. Int. J. Cancer 2008). In the present study, to investigate the involvement of stem cells in NPC, we performed immunohistochemical analyses to examine nitrative DNA lesions (8-nitroguanine) and several cancer stem / progenitor cell markers (CD44v6, CD24 and ALDH1A1) in nasopharyngeal tissues obtained from chronic nasopharyngitis and NPC patients. The staining intensity of 8-nitroguanine was significantly higher in cancer cells and inflammatory cells in stroma of NPC than in chronic nasopharyngitis tissues. Expression levels of CD44v6 and ALDH1A1 were significantly increased in cancer cells of primary NPC specimens in comparison to chronic nasopharyngitis tissues. 8-Nitroguanine was detected in CD44v6- or ALDH1A1-positive stem cells in NPC tissues. In the case of CD24 staining, there was no significant difference between NPC and chronic nasopharyngitis tissues. Intensive staining of CD44v6 and ALDH1A1 were also detected in NPC cell line HK1 compared to immortalized nasopharyngeal epithelial cells NP460 by a double immunofluorescence study and western blotting assay. In conclusion, CD44v6 and ALDH1A1 could be candidates of cancer stem cell markers for NPC. The present results indicate the possible mechanism by which inflammation causes NPC by inducing inflammatory processes and formation of 8-nitroguanine in CD44v6- and / or ALDH1A1-positive stem cells, and mutant stem cells participate in NPC development.

MP56-09 EXPRESSION PROFILE OF CD44S, CD44V6, AND CD44V10 IN LOCALIZED PROSTATE CANCER: IMPACT ON PROGNOSTIC OUTCOMES FOLLOWING RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized III1 Apr 2015MP56-09 EXPRESSION PROFILE OF CD44S, CD44V6, AND CD44V10 IN LOCALIZED PROSTATE CANCER: IMPACT ON PROGNOSTIC OUTCOMES FOLLOWING RADICAL PROSTATECTOMY Hiromoto Tei, Hideaki Miyake, and Masato Fujisawa Hiromoto TeiHiromoto Tei More articles by this author , Hideaki MiyakeHideaki Miyake More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2073AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES CD44 has been shown to play important roles in the progression of malignant tumors, including prostate cancer, by generating variant isoform through alternative splicing of variant exons, and its expression potentially influences stem cell behavior of cancer cells by a wide range of mechanisms. However, few data are available concerning the impact of CD44 expression on the prognosis of patients with prostate cancer, particularly those with localized disease. The objective of this study was to retrospectively evaluate the expression of CD44 standard form (CD44s) and two major variant exons (CD44v6 and CD44v10) in localized prostate cancer to determine the prognostic significance of these markers following radical prostatectomy. METHODS Expression levels of CD44s, CD44v6, and CD44v10 in radical prostatectomy specimens from 160 patients with clinically localized prostate cancer were evaluated by immunohistochemical staining. These findings were analyzed according to several clinicopathological outcomes, including biochemical recurrence (BR) which was defined as PSA of 0.2 ng/ml or greater on two consecutive measurements. In this series, irrespective of the pathological findings suggesting a poor prognosis, none of the patients were treated with any adjuvant therapies until their serum PSA values reached 0.4 ng/ml or greater. RESULTS Of these 3 markers, expression level of CD44v6 was closely associated with several conventional prognostic factors. Univariate analysis identified eight factors, including PSA level, Gleason score, extraprostatic extension, surgical margin status, lymphatic invasion, microvascular invasion, seminal vesicle invasion and CD44v6 expression, as significant risk factors for BR. Of these significant factors, PSA level, surgical margin status and CD44v6 expression were appeared to be independently associated with BR on multivariate analysis. There were significant differences in BR-free survival according to positive numbers of these 3 independent factors; that is, BR occurred in none of 42 patients who were negative for risk factors (0%), 9 of 54 positive for one risk factor (16.7%) and 31 of 64 positive for two or three risk factors (48.4%). CONCLUSIONS These findings suggest that the combined evaluation of the expression levels of CD44 variant exons, particularly CD44v6, in radical prostatectomy specimens with conventional prognostic parameters would contribute to the accurate prediction of BR following radical prostatectomy for clinically localized prostate cancer. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e684 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiromoto Tei More articles by this author Hideaki Miyake More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Detection and Clinical Significance of CD44v6 and Integrin-β1 in Pancreatic Cancer Patients using a Triplex Real-Time RT-PCR Assay

The cell adhesion molecules CD44v6 and integrin-β1 are associated with the progression and metastasis of cancer. A novel triplex real-time reverse transcription polymerase chain reaction (qRT-PCR) assay was developed to quantify CD44v6 and integrin-β1 gene expression in peripheral blood mononuclear cells from 30 pancreatic cancer (PC) patients and 12 healthy individuals. The standard curve of the triplex qRT-PCR was constructed by optimizing the reaction condition and the amplification efficiency was 102.5, 101.1, and 100.6 % for CD44v6, integrin-β1 and endogenous gene (β-actin) amplification. Nonspecific bands were not observed from the triplex qRT-PCR amplification and the detection limit of this assay was 100 copies. Expression levels of CD44v6 and integrin-β1 gene were significantly lower in healthy individuals than PC patients (P<0.05). CD44v6 and integrin-β1 gene expression were not associated with the sex, age, and tumor position in PC (P>0.05). CD44v6 gene expression was significantly associated with clinical stage, liver metastasis, and tumor size (P<0.05). Integrin-β1 gene expression was significantly associated with clinical stage and liver metastasis (P<0.05). This triplex qRT-PCR assay may provide a useful tool for diagnosis, prognosis, and therapeutic evaluation in PC.

Abstract 1527: CD44v9 involving in multiple myeloma cells adhesion to bone marrow stromal cell promotes bone erosion by augmenting the activation of HGF-receptor/cMet

Abstract The main aim of our study is to determine the significance of the stromal microenvironment in the malignant behavior of multiple myeloma cells. The stroma-derived growth factors/cytokines and hyaluronan act in autocrine/paracrine ways with their receptors, including receptor-tyrosine kinases and CD44 variants (CD44v), to potentiate and support multiple myeloma cell survival. In this study, we found that CD44s and CD44 variants were differentially expressed between fraction of CD138+ fraction and CD138- fraction. Expression levels of CD44v6, CD44v9, and CD44v10, respectively, correlated with bone erosion (p=0.029, p=0.013, p=0.032), suggesting that CD44 variant molecules are involved in multiple myeloma progression. Binding studies using CD44 isoform specific reagents showed that CD44v6 and CD44v9 were involved in binding to bone marrow stromal cells, but not to in vitro synthesized ECM. In 3D culture, CD44v6 and CD44v9-mediated plasma cell binding resulted in a significant induction of HGF secretion by bone marrow stromal cells. CD44v6 and CD44v9-mediated plasma cell binding significantly induces PI3K/Akt via activation the Src-kinase Lyn. In bone marrow serum of MM patients, the expression levels of IL-6, OPN, and hepatocyte growth factor (HGF), respectively, statistically correlated with bone erosion of MM patients (p=0.021, p=0.001, p=0.036). HGF derived from bone marrow stromal cells with multiple myeloma cells stimulates CD44 signaling via activation of HGF-receptor/cMet. Specific CD44 shRNA suppresses HGF-mediated CD44 signaling. Taken together, the role of CD44 variants in adhesion induced HGF- secretion may explain the previously observed correlation between CD44 variants expression and adverse prognosis in multiple myeloma. 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 1527. doi:1538-7445.AM2012-1527

The expression levels of CD44v6 are correlated with the invasiveness of hepatocellular carcinoma in vitro, but do not appear to be clinically significant.

The finding that the expression of a variant isoform of CD44 induced a metastatic phenotype in locally growing tumor cells has attracted considerable attention. A number of studies have analyzed the expression of CD44v6 in human tumors of different origins. However, the findings of these studies have been controversial. Therefore, in the present study, we assessed the association between CD44v6 expression and the invasive capacity of hepatocellular carcinoma (HCC) cell lines and also investigated the clinical significance of CD44v6 in 150 HCC patients by immunohistochemical analysis. The HCC cell lines with a high CD44v6 expression, including HLF, HLE and SK HEP-1, showed high invasive potential, whereas those with a low CD44v6 expression, including PLC/PRF/5 and HuH1, showed low invasiveness. Despite these observations, we did not find any significant correlation between CD44v6 expression and clinicopathological factors in patients. By contrast, there was a weak correlation between a low CD44v6 expression and vascular invasion in HCC patients (P=0.080). Kaplan-Meier curves revealed that a high CD44v6 expression was not significantly associated with disease-free survival (P=0.736) or overall survival (P=0.736). Our study suggests that the expression levels of CD44v6 are correlated with the invasiveness of HCC in vitro, but do not appear to be clinically significant. Future experiments should investigate the role of the various CD44 isoforms, including the CD44 standard isoform, in HCC cell lines and in patients with HCC.

Expression of CD44 variant isoforms CD44v3 and CD44v6 is increased on T cells from patients with systemic lupus erythematosus and is correlated with disease activity

To quantify the expression of CD44 and variant isoforms CD44v3 and CD44v6 on T cells from patients with systemic lupus erythematosus (SLE), and to assess correlations of the level of expression of these molecules with disease manifestations. Information on clinical and demographic characteristics was collected, and blood samples were obtained from 72 patients with SLE and 32 healthy control subjects matched to the patients by sex, race, and age. Expression of CD44 and variants CD44v3 and v6 on T cell subsets was determined by flow cytometry, and Pearson's correlations of their expression levels with clinical variables, SLE Disease Activity Index (SLEDAI) scores, and presence of lupus nephritis were determined. Wilcoxon's rank sum tests and conditional multivariable regression analyses were applied to identify differences in the expression of CD44 between patients with SLE and healthy controls. Expression of CD44 was higher on CD4+ and CD8+ T cells from SLE patients compared with controls (P <or= 0.03). Expression of CD44v3 and CD44v6 was also higher on total T cells and CD4+ and CD8+ T cells from SLE patients compared with controls (P <or= 0.03). Cell surface levels of CD44v3 on total T cells, CD4+ T cells, and CD8+ T cells as well as cell surface expression of CD44v6 on total T cells and CD4+ T cells were correlated with the SLEDAI score (P < 0.05). The presence of lupus nephritis was associated with the expression of CD44v6 on total T cells, CD4+ T cells, and CD4-CD8- T cells (P < 0.05). Positivity for anti-double-stranded DNA antibodies was associated with the expression levels of CD44v6 on T cells (P < 0.05). These results indicate that expression levels of CD44v3 and CD44v6 on T cells may represent useful biomarkers of SLE activity.

Expression of CD44v6 but not E-cadherin or beta-catenin influences prognosis in primary pulmonary adenocarcinoma.

Primary pulmonary adenocarcinoma was studied, looking for relationships between the expression of cell adhesion molecules (CAMs) E-cadherin, beta-catenin and CD44v6, and clinicopathological tumour parameters and patient post-operative survival. Formalin-fixed, paraffin-embedded tissue from 120 primary lung adenocarcinomas, including 23 poorly differentiated tumours, 17 of probable bronchial origin, and 29 with a prominent bronchioloalveolar pattern, together with nodal metastatic tumour from 34 of these patients was stained using monoclonal antibodies and immunohistochemistry. Sections were scored either high level (>10% cells positive) or low level (<10% positive). High level expression of CD44v6 was retained in 28.4% (34/120) of tumours, while high levels of E-cadherin (57.5%, 69/120) and beta-catenin (80. 8%, 97/120) were more frequent. For all CAMs, staining levels did not correlate with nodal status, stage or tumour type. The apical or basal staining seen in normal bronchial and alveolar epithelium was often seen in papillary, glandular, and bronchioloalveolar areas of tumour, while solid invasive tumour more often showed pericellular staining. When the staining for each CAM in 34 nodal metastases was compared with that in the corresponding primary tumour, a high degree of concordance was found, with no tendency for metastases to show less staining than the primary tumour. Expression of E-cadherin and beta-catenin in the primary tumour had no influence on post-operative survival, but patients whose tumours had low level CD44v6 expression had a poorer post-operative survival than those with high levels of CD44v6 (p=0.0014 for all patients, p=0.0012 for stage I patients only). In primary pulmonary adenocarcinoma, the levels of expression of E-cadherin, beta-catenin, and CD44v6 are not associated with lymph node metastases or tumour stage but the staining pattern is associated with tumour morphology. Low levels of CD44v6 expression predict a poor post-operative survival, independently of stage, while there is no such relationship with the expression of E-cadherin or beta-catenin.