Characterizing the Cells of Origin for Basal Cell Carcinoma

作为北美最常见的癌症，基底细胞癌(BCC)影响 每年有近一百万名新患者。目前，引起基底细胞癌的确切细胞 换句话说，正如多项研究所表明的那样，这些肿瘤的起源细胞目前尚不清楚。 报告的结果相互矛盾。在这笔赠款的K99阶段，我将伤人行为确定为 肿瘤细胞起源的调节剂。在没有损伤的情况下，毛囊干细胞在 隆起区不能形成由高转导癌基因诱导的肿瘤 Hedgehog(HH)级信令。然而，一旦这些干细胞受伤，它们就会离开 隆起并转移到损伤部位，在那里它们获得形成肿瘤的能力。建立在 这项先前的工作，这项赠款试图更详细地检查可能的起源细胞 BCC，以及影响肿瘤形成的信号通路。这样做的目的是 提案将包括确定1)Wnt，另一条重要的细胞信号通路， 与HH合作调节基底细胞癌的形成；2)干细胞是否位于头发中 卵泡峡部是否能够发展成肿瘤；以及3)一个重要的受体 CXCR4参与细胞迁移，在创伤诱导的基底细胞癌中发挥作用 肿瘤发生学。这些研究的总和可能会扩大我们对密件抄送的了解，以及 希望能增加我们对其他依赖于非调控HH信号的肿瘤的了解。

As the most frequently diagnosed cancer in North America, basal cell carcinoma (BCC) affects nearly a million new patients each year. At present, the exact cells that give rise to BCC¿in other words, the cells-of-origin for these tumors¿are currently unclear, as multiple studies have reported conflicting results. During the K99 phase of this grant, I identified wounding as a modulator of tumor cell-of-origin. In the absence of wounding, hair follicle stem cells in the bulge region are incapable of forming tumors induced by an oncogene that transduces high level Hedgehog (Hh) signaling. However, upon wounding these same stem cells leave the bulge and transit to the site of injury, where they gain the ability to form tumors. Building upon this previous work, this grant seeks to examine in greater detail the possible cells-of-origin for BCC, as well as the signaling pathways that impinge upon tumor formation. The Aims of this proposal will include determining whether 1) Wnt, another important cell signaling pathway, collaborates with Hh in modulating BCC formation; 2) whether stem cells located in the hair follicle isthmus are capable of developing tumors; and 3) whether an important receptor previously implicated in cell migration, CXCR4, plays a role in wound-induced BCC tumorigenesis. The sum of these studies will likely expand our knowledge of BCC, and hopefully increase our understanding of other tumors that rely upon deregulated Hh signaling.