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）影响着 每年新增近百万患者目前，引起BCC的确切细胞在 换句话说，这些肿瘤的起源细胞目前尚不清楚，因为多项研究已经证明， 报告了相互矛盾的结果。在K99阶段，我将伤害确定为 肿瘤细胞起源的调节剂。在没有创伤的情况下， 隆突区不能形成由癌基因诱导的肿瘤， 水平Hedgehog（Hh）信号传导。然而，一旦受伤，这些干细胞就会离开皮肤。 隆起并转移到损伤部位，在那里它们获得形成肿瘤的能力。基础上 这项先前的工作，这项赠款旨在更详细地研究可能的细胞起源， BCC，以及影响肿瘤形成的信号通路。这件事的目的 建议将包括确定1）Wnt，另一个重要的细胞信号通路， 与Hh合作调节BCC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）是否是重要的受体 先前与细胞迁移有关的CXCR 4在创伤诱导的BCC中起作用 肿瘤发生这些研究的总和可能会扩大我们对BCC的了解， 希望能增加我们对其他依赖Hh信号失调的肿瘤的理解。

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.