Cancer Progeniyor Cell Markers

描述(由申请人提供)：响应RFA-CA-08-011“癌症创新和应用分子分析技术(SBIR[R43/R44])”的第一阶段/第二阶段快速应用：“癌症前体细胞标记物”已在上皮性癌症患者的外周血中鉴定出循环肿瘤细胞(CTCs)。最近的研究表明，CTCs可能是一种潜在的替代活检的肿瘤组织来源，用于检测、表征和监测非血液病癌症。然而，目前分离CTCs的策略仅限于基于上皮细胞表面标志物的复杂分析方法。由于缺乏肿瘤细胞的特异性标记物，CTCs的分子同一性仍有待研究。我们推测，在Vitatex开发的细胞黏附矩阵(CAM)涂层设备分离、鉴定和增殖CTCs的能力可以导致识别新的癌症干细胞或前体细胞标记物，并扩大对肿瘤进展和转移机制的理解。为了满足这一需求，该团队最近解决的一组CTC上调的肿瘤前体细胞标志物将被用于提高上皮性卵巢癌患者CTC检测的特异性和敏感性，以及评估CTC在卵巢肿瘤腹膜转移中的潜在作用。首先，我们将选择新的肿瘤前体和侵袭性标志物，并通过荧光显微成像验证其性能来优化基于细胞的流式细胞仪血液检测，以提高CTC检测的敏感性和特异性。然后，我们将开发一种基于核酸的血液测试，使用多基因定量PCR分析中的肿瘤前体细胞标志物小组，对在石溪大学医学中心接受治疗的表型卵巢癌患者进行检测，并监测治疗反应。为了评估CTCs在转移进展中的相关性，通过使用实验性的卵巢转移动物模型，将通过CAM黏附和肿瘤前体基因的表达来分选细胞，以检测其进展为腹膜、肝脏和肺转移的能力。商业化的目标是制造一种有效的稀有细胞分离系统，作为外周血液中上皮癌分子分析的研究工具，并开发一种新的血液测试产品，使其能够对癌症进行更灵敏的诊断和预后评估，特别是与其转移潜力有关的评估。

DESCRIPTION (provided by applicant): "Cancer progenitor cell markers" Phase I/II Fast-Track application In response to RFA-CA-08-011 "Innovative and Applied Molecular Analysis Technologies for Cancer (SBIR [R43/R44])" Circulating tumor cells (CTCs) have been identified in peripheral blood from patients with epithelial cancers. Recent studies suggest that CTCs could represent a potential alternative to biopsies as a source of tumor tissue for the detection, characterization and monitoring of non-hematologic cancers. However, current strategies for isolating CTCs are limited to complex analytic approaches based on epithelial cell surface markers. Since markers specific for cancer cells are lacking, the molecular identity of CTCs remains to be investigated. We postulate that the ability of cell adhesion matrix (CAM)-coated devices developed in Vitatex to isolate, characterize and propagate CTCs could lead to the identification of novel cancer stem or progenitor cell markers and expand the understanding of the mechanism of tumor progression and metastasis. To address this need, a panel of tumor progenitor cell markers upregulated in CTCs that were recently resolved by this team will be used to improve the CTC detection specificity and sensitivity in patients with epithelial ovarian cancer, as well as to evaluate the potential role of CTCs in ovarian tumor peritoneal metastasis. Initially we will select novel tumor progenitor and invasiveness markers and optimize a cell-based flow cytometry blood test by validating its performance using fluorescence microscopic imaging to improve the sensitivity and specificity of CTC detection. We will then develop a nucleic acid-based blood test using a focused panel of tumor progenitor cell markers in multigene quantitative PCR analysis to phenotype patients with ovarian cancer who are treated at the Stony Brook University Medical Center and to monitor treatment response. To evaluate the relevance of CTCs in metastatic progression, cells sorted by both CAM adhesion and expression of a tumor progenitor gene will be examined for their ability to progress into peritoneal, liver and lung metastases by using an experimental ovarian metastasis animal model. The commercialization objectives are to manufacture an efficient rare cell separation system as a research tool for molecular analysis of epithelial cancers in peripheral blood, and to develop a novel blood test product that allows more sensitive diagnostic and prognostic evaluation of cancer, particularly relating to its metastatic potential.