The CEA-/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells.
The CEA-/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells.
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CEA-/lo结直肠癌细胞群含有癌症干细胞和转移细胞。
DOI：
10.18632/oncotarget.13029
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发表时间：
2016-12-06
期刊：
影响因子：
--
通讯作者：
Qin J
中科院分区：
文献类型：
--
作者：
Yan C;Hu Y;Zhang B;Mu L;Huang K;Zhao H;Ma C;Li X;Tao D;Gong J;Qin J
血清癌胚抗原（CEA）是包括结直肠癌（CRC）在内的多种癌症中最常用的肿瘤标志物，用于肿瘤诊断和监测。最近的研究表明，表达很少或不表达 CEA 的结肠隐窝细胞可能富含干细胞。大量研究清楚地表明，尽管CEA本身被认为具有促进转移和阻断细胞分化的作用，但在肿瘤进展甚至肿瘤复发过程中，存在着CRC患者血清CEA水平正常的情况。这些看似矛盾的观察结果促使我们在此研究表达高 (CEA+) 与低 (CEA-/lo) 水平 CEA 的 CRC 细胞的生物学特性以及致瘤和转移能力。我们的研究结果表明，CEA−/lo 细胞的丰度与分化不良和预后不良相关，而且，与相应的 CEA+ 细胞相比，CEA−/lo 细胞在体外形成更多的球体，产生更多的肿瘤，并表现出更高的发生肝和肺转移的潜力。应用RNAi介导的方法，我们发现IGF1R介导CEA−/lo细胞的致瘤性和能力，但不介导CEA+细胞的致瘤性和能力。值得注意的是，我们的数据表明CEA分子能够保护CEA−/lo细胞免受失巢凋亡，这意味着CEA+细胞虽然本身具有较低的致瘤和转移能力，但可能通过分泌CEA分子促进CEA−/lo细胞的转移。我们的观察表明，除了靶向 CEA 分子外，CEA−/lo 细胞可能代表肿瘤进展和转移的关键来源，因此应该成为未来治疗的目标。
Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA−/lo) levels of CEA. Our findings show that the abundance of CEA−/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA−/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA−/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA−/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA−/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA−/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies.