Bone Marrow-Derived Cells Are Not the Origin of the Cancer Stem Cells in Ultraviolet-Induced Skin Cancer

Bone Marrow-Derived Cells Are Not the Origin of the Cancer Stem Cells in Ultraviolet-Induced Skin Cancer
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DOI:
10.2353/ajpath.2009.080362
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发表时间:
2009-02-01
影响因子:
6
通讯作者:
Shimizu, Hiroshi
Shimizu, Hiroshi
中科院分区:
医学2区
文献类型:
--
作者:
Ando, Satomi;Abe, Riichiro;Shimizu, Hiroshi

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许多证据表明,多种癌症来源于癌干细胞(CSCs),而CSCs被认为来源于组织干细胞或祖细胞。然而,最近的研究表明,CSC的起源可能是骨髓来源的细胞(BMDC);例如,胃癌,持续性胃炎症,似乎起源于BMDC。虽然我们以前的研究表明BMDCs有能力分化为表皮角质形成细胞,但皮肤CSC是否起源于BMDCs尚未确定。为了评估BMDC可能是皮肤鳞状细胞癌(SCC)中CSC起源的可能性,我们使用了UVB诱导的皮肤SCC小鼠模型。我们在表皮发育不良(0.59%)、原位SCC(0-15%)和SCC(0-03%)病变中检测到低百分比的BMDC。此外,我们没有发现任何克隆BMDC扩增的证据。在SCC病变中,我们还发现大多数BMDC是肿瘤浸润的造血细胞。此外,SCC病变中的BMDC缺乏表皮干细胞的特征,包括干细胞标志物(CD 34,高α 6整合素)的表达和BrdU标记的潜在保留。这些结果表明,BMDCs不是UVB诱导的SCC中恶性角质形成细胞的主要来源。因此,我们的结论是,BMDCs是不是在UVB诱导的SCC中的CSC的起源。(Am J Pathol 2009,174:595-601; DOI:10.2353/ajpath.2009.080362)
Several lines of evidence have demonstrated that various cancers are derived from cancer stein cells (CSCs), which are thought to originate from either tissue stem or progenitor cells. However, recent studies have suggested that the origin of CSCs could be bone marrow-derived cells (BMDCs); for example, gastric cancer, which follows persistent gastric inflammation, appears to originate from BMDCs. Although our previous research showed the capability of BMDCs to differentiate into epidermal keratinocytes, it has yet to be determined whether skin CSCs originate from BMDCs. To assess the possibility that BMDCs could be the origin of CSCs in skin squamous cell carcinoma (SCC), we used a mouse model of UVB-induced skin SCC. We detected a low percentage of BMDCs in the lesions of epidermal dysplasia (0.59%), SCC hi situ (0-15%), and SCC (0-03%). Furthermore, we could not find any evidence of clonal BMDC expansion. In SCC lesions, we also found that most of the BMDCs were tumor-infiltrating hematopoietic cells. in addition, BMDCs in the SCC lesions lacked characteristics of epidermal stem cells, including expression of stem cell markers (CD34, high alpha 6 integrin) and the potential retention of BrdU label. These results indicate that BMDCs are not a major source of malignant keratinocytes in UVB-induced SCC. Therefore, we conclude that BMDCs are not the origin of CSCs in UVB-induced SCC. (Am J Pathol 2009, 174:595-601; DOI: 10.2353/ajpath.2009.080362)