A Novel Marker for Undifferentiated Human Embryonic Stem Cells

Higashi, Kei; Yagi, Masahide; Arakawa, Tatsuhiko; Asano, Koji; Kobayashi, Kumiko; Tachibana, Taro; Saito, Koichi

doi:10.1089/mab.2014.0075

Cited by 8 publications

(7 citation statements)

References 23 publications

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“…21 CD147/EMMPRIN is an important marker for anchorage independent growth, angiogenesis, drug resistance, hypoxic survival, and invasion, properties attributed to CSCs and which are essential molecular events for carcinogenesis. 22 Additionally, CD147 is also a marker of undifferentiated human embryonic stem cells 23 and has been reported as a marker of oral CSCs. 24 Recent studies have implicated CD147, along with CD44, in modulation of the Wnt/β-catenin pathway 25 in metastatic prostate cancer, a property which is being investigated as potential therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma

et al. 2017

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Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p < 0.01). Furthermore, co-expression analysis showed that 45% each of moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44/CD147 as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p < 0.05) in only the patients with CD44/CD147 cohort. Subsequently, relevance of these cancer stem cell markers in patterning the differentiation characteristics was evaluated in oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44/CD147 cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p < 0.001) and moderately differentiated squamous cell carcinoma origin (93.49 ± 0.47%, p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial-mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin. This study suggests that CD44 and CD147 together improve the prognostic efficacy of tumor differentiation; in vitro results further point out that these markers might be determinant of differentiation characteristics, imparting properties of increased self-renewal, migration, and invasion.

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Section: Discussionmentioning

confidence: 99%

Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma

et al. 2017

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“…As an adhesion molecule, CD147 is widely expressed in a variety of cancer types. Recently, Higashi et al (29) demonstrated that CD147 may be an undifferentiated marker of human embryonic stem cells. Despite substantial progress of CD147 in cancer pathogenesis, the biological roles of CD147 are not clear in CSCs.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells

Chen

Pan

et al. 2015

International Journal of Oncology

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Abstract.The association between CD147 and cancer stem cells (CSCs) provides a new angle for cancer treatments. The aim of this study was to investigate the biological roles of CD147 in colorectal CSCs. The Oct4-green fluorescent protein (GFP) vector was used to isolate CSCs and pYr-mir30-shRNA was used to generate short hairpin RNA (shRNA) specifically for CD147. After RNA interference (RNAi), CD147 was evaluated by reverse transcription-quantitative PCR and western blot analysis, and its biological functions were assessed by MTT and invasion assays. The results showed that the differentiation of isolated CSC-like HT-29 cells was blocked and these cells were highly positive for CD44 and CD147. RNAi-mediated CD147 silencing reduced the expression of CD147 at both mRNA and protein levels. Moreover, the activities of proliferation and invasion were decreased obviously in CSCs. Knockdown of CD147 increased the chemosensitivity of CSC-like cells to gemcitabine, cisplatin, docetaxel at 0.1, 1 and 10 µM respectively, however, there was no significant difference among the three groups to paclitaxel at 10 µM. In conclusion, these results suggest that CD147 plays an important role in colorectal CSCs and might be regarded as a novel CSC-specific targeted strategy against colorectal cancer. IntroductionColorectal cancer, one of the three most common malignancies in the world, remains a major public health problem (1). In 2014, an estimated 71,830 men and 65,000 women were diagnosed with colorectal cancer and 26,270 men and 24,040 women will die of the disease (2). In recent years, remarkable advances have been made in colorectal cancer therapeutic approaches by using chemotherapy, radiotherapy, monoclonal antibodies and small-molecule inhibitors. However, the clinical outcome was far from expected as the effects of these improvements never continued for a long duration (3,4). Therefore, new and better therapies will be the key to reducing the incidence of colorectal cancer.A new emerging concept implicates that treatment failure occurs due to the existence of cancer stem cells (CSCs) that evade the treatment regimen (5,6). These cells had been characterized by pluripotency, self-renewal as well as tumorigenicity (7-9). CSCs were resistant to traditional therapies, leading to tumor recurrence and unpleasant prognosis for cancer patients (10,11). Conventional treatments mainly targeted the tumor cells, but not the CSCs. Thus, therapeutic strategies specifically targeting CSCs could eradicate colorectal cancer more effectively.CSCs were firstly identified in hematopoietic tumors by using cell surface and intracellular molecules (12). Also other types of tumors have been examined for CSCs (13-16). Many studies had chosen specific cell surface markers such as CD19, CD20, CD24, CD44 and CD133 to characterize the subpopulation of CSCs. Transcription factor Oct4 was also typically an intracellular marker (7,(17)(18)(19). Oct4 (also known as OCT3, OCT3/4) belongs to the POU (Pit-Oct-Unc) family of transcription factors. It can form...

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“…Cultures of Oct-4 lung stem cells could be infected with SARS-CoV with subsequent virus replication, suggesting that failing lung repair of SARS-CoVinfected involves the loss of mobilization and differentiation of lung stem and progenitor cells. On the other hand, CD147, the second entry receptor for SARS-CoV-2, has been proposed to be a marker protein of undifferentiated embryonic stem cells, and the monoclonal antibody against this protein also stained lung cancer cells [29]. It is possible that CD147 is also expressed by untransformed lung stem and progenitor cells; however, to the best of our knowledge, there is no experimental evidence for such affirmation.…”

Section: Stem Cell Facets In Covid-19: Possible Target For Infectionmentioning

confidence: 95%

CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement

Ulrich

Pillat

2020

Stem Cell Rev and Rep

392

417

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The expressive number of deaths and confirmed cases of SARS-CoV-2 call for an urgent demand of effective and available drugs for COVID-19 treatment. CD147, a receptor on host cells, is a novel route for SARS-CoV-2 invasion. Thus, drugs that interfere in the spike protein/CD147 interaction or CD147 expression may inhibit viral invasion and dissemination among other cells, including in progenitor/stem cells. Studies suggest beneficial effects of azithromycin in reducing viral load of hospitalized patients, possibly interfering with ligand/CD147 receptor interactions; however, its possible effects on SARS-CoV-2 invasion has not yet been evaluated. In addition to the possible effect in invasion, azithromycin decreases the expression of some metalloproteinases (downstream to CD147), induces anti-viral responses in primary human bronchial epithelial infected with rhinovirus, decreasing viral replication and release. Moreover, resident lung progenitor/stem are extensively differentiated into myofibroblasts during pulmonary fibrosis, a complication observed in COVID-19 patients. This process, and the possible direct viral invasion of progenitor/stem cells via CD147 or ACE2, could result in the decline of these cellular stocks and failing lung repair. Clinical tests with allogeneic MSCs from healthy individuals are underway to enhance endogenous lung repair and suppress inflammation.

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A Novel Marker for Undifferentiated Human Embryonic Stem Cells

Cited by 8 publications

References 23 publications

Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma

Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma

Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells

CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement

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