کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1941587 1536900 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
High-throughput flow cytometry screening of human hepatocellular carcinoma reveals CD146 to be a novel marker of tumor-initiating cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
High-throughput flow cytometry screening of human hepatocellular carcinoma reveals CD146 to be a novel marker of tumor-initiating cells
چکیده انگلیسی


• Unbiased screens of human HCC cells for novel TIC markers have not been reported.
• A high-throughput flow cytometry screen of human HCC cells was successfully performed .
• Candidate TIC markers were further evaluated by RT-PCR and functional assays.
• Of candidates tested, only CD146 expression was significantly increased in HCC tissues.
• CD146+ cells had increased colony-forming capacity, consistent with a TIC phenotype.

Hepatocellular carcinoma (HCC) remains a common and lethal cancer. Cancer stem cells, or tumor-initiating cells (TICs), are thought to contribute to the pathogenesis of HCC, but remain to be fully characterized. Unbiased screens of primary human HCC cells for the identification of novel HCC TIC markers have not been reported. We conducted high-throughput flow cytometry (HT-FC) profiling to characterize the expression of 375 CD antigens on tumor cells from 10 different human HCC samples. We selected 91 of these for further analysis based on HT-FC data that showed consistent expression in discrete, rare, sortable populations of HCC cells. Nine of these CD antigens demonstrated significantly increased expression in the EpCAM+ stem/progenitor fraction of a human HCC cell line and were further evaluated in primary human HCC tissues from 30 different patients. Of the nine tested, only CD146 demonstrated significantly increased expression in HCC tumor tissue as compared with matched adjacent non-tumor liver tissue. CD146+CD31−CD45− cells purified from HCC tumors and cell lines demonstrated a unique phenotype distinct from mesenchymal stem cells. As compared with other tumor cell fractions, CD146+CD31−CD45− cells showed significantly increased colony-forming capacity in vitro, consistent with TICs. This study demonstrates that HT-FC screening can be successfully applied to primary human HCC and reveals CD146 to be a novel TIC marker in this disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemistry and Biophysics Reports - Volume 8, December 2016, Pages 107–113
نویسندگان
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