Expression Of Mdr-Transporter, Abcb5, In Merkel Cell Carcinoma

FASEB JOURNAL(2013)

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摘要
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine neoplasm notoriously refractory to chemotherapy. We have previously found that the multidrug resistance (MDR) transporter, ABCB5, mediates drug resistance in human colonic adenocarcinoma and melanoma where it also defines stem‐like cells responsible for tumor initiation and self‐renewal. The aim of this study was to evaluate the possible role of ABCB5 in MCC. Primary and metastatic MCCs (n=74) were assessed for ABCB5, and mRNA expression and immunoreactivity was confirmed in all cases. Of note, co‐expression of ABCB5 with stem cell markers SOX2 and CD271 was documented in a subset of MCC cells in human tissue, while CD44 and ABCB5 defined separate cell populations. ABCB5 + cells were enriched in patient biopsies after chemotherapy, consistent with relative chemoresistance of this tumor cell subset. In cell line‐derived MCC xenografts in NSG mice, tumors formed by WaGa and MKL‐1 cells demonstrated increased ABCB5 expression after administration of etoposide or carboplatin. In summary, MCCs express ABCB5, and this biomarker may have functional significance regarding both chemoresistance and tumorigenic potential. NIH P50CA93683, Dermatology Foundation Career Development Award and BWH Dermatology new investigator funding.
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关键词
abcb5,carcinoma
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