• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8679-8684
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• 2014

CD133 was recently reported to be a cancer stem cell and prognostic marker. Quercetin is considered as a potential chemopreventive agent due to its involvement in suppression of oxidative stress, proliferation and metastasis. In this study, the expression of CD133/CD44 in esophageal carcinomas and Eca109/9706 cells was explored. In immunoflurorescence the locations of $CD133^+$ and multidrug resistance 1 $(MDR1)^+$ in the same E-cancer cells were coincident, mainly in cytomembranes. In esophageal squamous cell carcinomas detected by double/single immunocytochemistry, small $CD133^+$ cells were located in the basal layer of stratified squamous epithelium, determined as CSLC (cancer stem like cells); $CD44^+$ surrounding the cells appeared in diffuse pattern, and the larger $CD44^+$ (hi) cells were mainly located in the prickle cell layer of the epithelium, as progenitor cells. In E-cancer cells exposed to nanoliposomal quercetin (nLQ with cytomembrane permeability), down-regulation of NF-${\kappa}Bp65$, histone deacetylase 1 (HDAC1) and cyclin D1 and up-regulation of caspase-3 were shown by immunoblotting, and attenuated HDAC1 with nuclear translocation and promoted E-cadherin expression were demonstrated by immunocytochemistry. In particular, enhanced E-cadherin expression reflected the reversed epithelial mesenchymal transition (EMT) capacity of nLQ, acting as cancer attenuator/preventive agent. nLQ acting as an HDAC inhibitor induced apoptotic cells detected by TUNEL assay mediated via HDAC-NF-${\kappa}B$ signaling. Apoptotic effects of liposomal quercetin (LQ, with cytomembrane-philia) combined with CD133 antiserum were also detected by CD133 immunocytochemistry combined with TUNEL assay. The combination could induce greater apoptotic effects than nLQ induced alone, suggesting a novel anti-CSC treatment strategy.

• 대한수의학회지
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• 제58권1호
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• pp.33-37
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• 2018

Various trials have been conducted to develop therapies for serious untreatable diseases. Among these, those using stem cells have shown great promise, and adipose-derived mesenchymal stem cells (ADMSCs) are easier to obtain than other types of stem cells. Prior to clinical trials, characterization of ADMSCs with monoclonal antibodies should be performed. However, it is difficult to use species-specific antibodies for veterinarians. This study was conducted to confirm the panel of human antibodies applicable for use in immunophenotypic characterization of canine adipose-derived stem cells and feline ADMSCs extracted from subcutaneous adipose tissue collected during ovariohysterectomy. For flow cytometric immunophenotyping, the third passages of canine ADMSC and feline ADMSC and human CD31, CD34, CD42, CD44, CD62 and CD133 antibodies were used. Of these, CD133 reacted with canine cells (3.74%) and feline cells (1.34%). CD133 is known as a marker related with more primitive stem cell phenotype than other CD series. Because this human CD133 was not a species-specific antibody, accurate percentages of immunoreactivity were not confirmed. Nevertheless, the results of this study confirmed human CD133 as a meaningful marker in canine and feline ADMSCs.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8161-8169
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• 2014

Background: Cancer stem cells (CSC) are populations of cells responsible for tumor initiation, progression and therapeutic resistance in many cancers. In the present study, we aimed to investigate the expression pattern and clinical significance of two CSC markers, CD133 and Nestin, in a series of skin tumors. Materials and Methods: One hundred and thirteen paraffin blocks from skin cancers including 16 (14%) cases of melanoma, 37 (33%) of squamous cell cancer (SCC) and 60 (53%) of basal cell cancer (BCC) were collected and assembled in a tissue microarray (TMA). The samples were immunohistochemically examined for the expression of CD133 and Nestin. Expression of these markers was also correlated with clinicopathological parameters. Results: A significant difference was observed in the expression of CD133 and Nestin in melanomas, SCC and BCC (p value=0.001). Furthermore, the level of expression was significantly higher in the melanomas compared to the SCC and BCC tumors. Expression of CD133 in the melanoma was significantly associated with increased tumor invasiveness (p value=0.05), a higher rate of metastasis (p value=0.04) and the presence of ulceration (p value=0.02). Increased expression of Nestin was observed in metastatic melanoma (p value=0.04), while no statistically significant correlation was found with other clinicopathological parameters including Breslow thickness, Clark level and ulceration. Conclusions: Elevated expression levels of CD133 and Nestin in the melanomas are associated with advanced disease, with more aggressive and metastatic skin tumors. Therefore, these markers could be potential therapeutic targets for malignant tumors of the skin.

• 한국재료학회:학술대회논문집
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• 한국재료학회 1998년도 추계학술발표강연 및 논문개요집
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• pp.133-133
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• 1998

• Nutrition Research and Practice
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• 제16권2호
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• pp.161-172
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• 2022

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness. MATERIALS/METHODS: CD133⁺CD44⁺ HCT116 and CD133⁺CD44⁺ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133⁺CD44⁺ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors. RESULTS: BC inhibited self-renewal capacity and CSC markers, including CD44, CD133, ALDH1A1, NOTCH1, Sox2, and β-catenin in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133⁺CD44⁺ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed in vivo as well. CONCLUSIONS: These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.

• 한국재료학회:학술대회논문집
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• 한국재료학회 2007년도 추계학술발표대회 및
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• pp.133.2-133.2
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• 2007

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4177-4183
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• 2015

Background: Gastric cancer is the second leading cause of cancer-related death in Asia, and the majority type is gastric adenocarcinoma (GAC). Most GAC patients die of recurrence and metastasis. Cancer stem cells (CSCs) have been thought to be responsible for the initiation, development, metastasis, and ultimately recurrence of cancer. In this study, we aimed to investigate expression and clinical significance of CSCs markers, CD133 and Lgr5, and vasculogenic mimicry (VM) in primary GAC. Materials and Methods: Specimens from 261 Chinese patients with follow-up were analyzed for CD133, Lgr5 protein expression and VM by immunohistochemical and histochemical staining. The Pearson Chi's square test was used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time was were studied by univariate and multivariate analyses. Results: In GAC tissues, positive rates of 49.0%, 38.7%, and 26.8% were obtained for CD133, Lgr5, and VM, respectively. The mean score of microvessel density (MVD) was $21.7{\pm}11.1$ in GAC tissues. There was a significantly difference between the positive and negative groups. There was a positive relationship between the VM, the expression of CD133 and Lgr5, and the score of MVD and the grades of tumor, lymph node metastasis, TNM stages (all p<0.05). The overall mean survival time of the patients with CD133, Lgr5, VM, and MVD (${\geq}22$) positive expression was lower than that of patients with negative expression. The score of MVD, positive expression of CD133 and VM were independent prognostic factors of GAC (p<0.05). Conclusions: VM, and expression of CD133, Lgr5, and the score of MVD are related to grades of tumor, lymph node metastasis, TNM stages, and overall mean survival time. It is suggested that CSCs and VM could play an important role in the evolution of GAC.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1023-1035
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• 2016

The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemically-induced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4849-4852
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• 2015

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been investigated as an effective agent to treat various cancers. Cancer stem cells are resistant to TRAIL treatment, but the mechanism of TRAIL resistance remains unknown. In this study, brain cancer stem cells were isolated by CD133 magnetic sorting, and the number of CD133 positive cells detected by flow cytometry. The self-renewing capacity of brain cancer stem cells was examined by a neurosphere formation assay, and the percentage of cell death after TRAIL treatment was examined by an MTS assay. Expression of DR5, FADD, caspase 8 and BCL2 proteins was detected by western blot. The amount of CD133 positive cells was enriched to 71% after CD133 magnetic sorting. Brain cancer stem cell neurosphere formation was significantly increased after TRAIL treatment. TRAIL treatment also reduced the amount of viable cells and this decrease was inhibited by a caspase 8 inhibitor or by the pan-caspase inhibitor z-VAD (P<0.05). Brain cancer stem cells expressed lower levels caspase 8 protein and higher levels of BCL2 protein when compared with CD133 negative cells (P<0.05). Our data suggest that TRAIL resistance is related to overexpression of BCL2 and low expression of caspase 8 which limit activation of caspase 8 in brain cancer stem cells.

• BMB Reports
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• 제48권3호
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• pp.127-128
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• 2015

Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.