Characterizing the Cells of Origin for Basal Cell Carcinoma

基底细胞癌起源细胞的特征

基本信息

批准号：
8698712
负责人：
Sunny Y Wong
金额：
$ 23.63万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2015-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8698712
关键词：
Affect Alleles Basal cell carcinoma CXCL12 gene CXCR4 gene Cells Competence Conflict (Psychology)Dermal Epidermis Erinaceidae Fibroblasts Future Germ Grant Hair Hair Follicle Isthmus Hair follicle structure Injury Knowledge Left Ligands Mediating Morphogenesis Movement Mus Neoplasm Metastasis Neural Crest Cell North America Oncogenes Pathway interactions Patients Phase Phenotype Play Population Process Publishing Reporting Role Signal Pathway Signal Transduction Site Skin Skin Cancer Stem cells Stromal Cell-Derived Factor 1 Sum Testing Work Wound Healing cancer diagnosis cell motility chemokine receptor inhibitor/antagonist keratinocyte leukocyte homing loss of function mutation migration neoplastic cell promoter receptor recombinase skin morphogenesis smoothened signaling pathway stem cell population tumor tumorigenesis tumorigenic wound

项目摘要

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.

作为北美最常诊断的癌症，基底细胞癌 (BCC) 影响着目前，每年有近百万新患者出现BCC。在换句话说，这些肿瘤的起源细胞？目前尚不清楚，因为多项研究表明在本次拨款的 K99 阶段，我报告了相互矛盾的结果。肿瘤细胞起源的调节剂在没有受伤的情况下，毛囊干细胞。凸起区域不能形成由转导高值的癌基因诱导的肿瘤然而，在受伤时，这些相同的干细胞会离开刺猬水平（Hh）信号。凸起并转移到受伤部位，在那里它们获得形成肿瘤的能力。在之前的工作中，这笔赠款旨在更详细地研究可能的起源细胞 BCC，以及影响肿瘤形成的信号通路。该提案将包括确定是否 1) Wnt，另一个重要的细胞信号传导途径，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形成肿瘤；3) 是否是重要的受体 CXCR4 先前与细胞迁移有关，在伤口诱导的 BCC 中发挥作用这些研究的总和可能会扩展我们对 BCC 的认识，以及希望能增加我们对依赖 Hh 信号失调的其他肿瘤的了解。