Characterization of the intestinal cancer stem cell marker CD166 in the human and mouse gastrointestinal tract.

Characterization of the intestinal cancer stem cell marker CD166 in the human and mouse gastrointestinal tract.
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DOI:
10.1053/j.gastro.2010.08.053
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发表时间:
2010-12
期刊:
影响因子:
29.4
通讯作者:
Wong MH
Wong MH
中科院分区:
医学1区
文献类型:
--
作者:
Levin TG;Powell AE;Davies PS;Silk AD;Dismuke AD;Anderson EC;Swain JR;Wong MH

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CD166(也称为活化白细胞粘附分子,ALCAM)是结直肠癌(CRC)干细胞的标志物;它由侵袭性肿瘤表达。尽管肿瘤细胞表面存在 CD166 与生存期缩短相关,但对其在正常肠上皮细胞中的功能和表达知之甚少。我们使用免疫组织化学、流式细胞术和定量逆转录 PCR 来表征人类和小鼠正常肠道组织样本中 CD166 的表达模式。还分析了人类和小鼠肠道肿瘤。 CD166 在干细胞生态位内的上皮细胞表面以及沿着肠道的长度上表达;表达在物种间是保守的。在小肠中,在基于隐窝的潘氏细胞和介入的基于隐窝的柱状细胞(假定的干细胞)上观察到 CD166。 CD166 阳性、基于隐窝的柱状细胞亚群共表达干细胞标记物 Lgr5、Musashi-1 或 Dcamkl-1。 CD166 位于人类结直肠癌肿瘤内的细胞质和细胞表面。在小鼠良性腺瘤中也检测到了 CD166 阳性细胞;罕见细胞共表达 CD166 和 CD44 或上皮特异性抗原。 CD166 在内源性肠干细胞生态位中高度表达。 CD166 阳性细胞出现在肠癌进展的多个阶段,包括良性和转移性肿瘤。进一步的研究应该调查 CD166 在干细胞和干细胞生态位中的功能,这可能对正常的肠道稳态具有影响。 CD166 有潜力作为 CRC 的治疗靶点。
CD166 (also called activated leukocyte cell adhesion molecule, ALCAM) is a marker of colorectal cancer (CRC) stem cells; it is expressed by aggressive tumors. Although the presence of CD166 at the tumor cell surface has been correlated with shortened survival, little is known about its function and expression in normal intestinal epithelia. We characterized the expression pattern of CD166 in normal intestinal tissue samples from humans and mice using immunohistochemisty, flow cytometry and quantitative reverse transcription PCR. Human and mouse intestinal tumors were also analyzed. CD166 was expressed on the surface of epithelial cells within the stem cell niche and along the length of the intestine; expression was conserved across species. In the small intestine, CD166 was observed on crypt-based Paneth cells and intervening crypt-based columnar cells (putative stem cells). A subset of CD166-positive, crypt-based columnar cells co-expressed the stem cell markers Lgr5, Musashi-1, or Dcamkl-1. CD166 was located in the cytoplasm and at the surface of cells within human CRC tumors. CD166-positive cells were also detected in benign adenomas in mice; rare cells co-expressed CD166 and CD44 or epithelial-specific antigen. CD166 is highly expressed within the endogenous intestinal stem cell niche. CD166-positive cells appear at multiple stages of intestinal carcinoma progression, including benign and metastatic tumors. Further studies should investigate the function of CD166 in stem cells and the stem cell niche, which might have implications for normal intestinal homeostasis. CD166 has potential as a therapeutic target for CRC.
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