Functional Significance of CD133 in Pancreatic Cancer

CD133 在胰腺癌中的功能意义

• 批准号: 8671286
• 负责人: Sulagna Banerjee
• 金额: $ 31.54万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8671286
• 关键词: Adenocarcinoma Cell; Affect; Aftercare; Animal Model; Animals; Applications Grants; Biological; Biological Assay; Biological Process; CXCR4 gene; Cancer Etiology; Cancer cell line; Cell Line; Cell physiology; Cell surface; Cells; Cessation of life; Characteristics; Data; Development; Disease; Down-Regulation; Evaluation; Event; Grant; In Vitro; Invaded; Laboratories; Lead; Malignant neoplasm of pancreas; Membrane Proteins; Molecular; Neoplasm Metastasis; Organ; Pancreas; Pancreatic Ductal Adenocarcinoma; Pathway interactions; Patients; Phase I Clinical Trials; Phenotype; Play; Population; Prevention; Prodrugs; Property; Proteins; Recurrence; Regimen; Regulation; Relapse; Reporting; Resistance; Role; Staging; Surface; Survival Rate; Therapeutic; Time; Tumor Cell Invasion; Tumor Markers; Tumorigenicity; United States; Up-Regulation; Variant; Water; analog; base; cancer cell; cancer stem cell; chemotherapeutic agent; chemotherapy; improved; in vivo; migration; mouse model; novel; outcome forecast; overexpression; pancreatic cancer cells; pancreatic neoplasm; preclinical study; prevent; public health relevance; stem; translational study; treatment strategy; triptolide; tumor; tumor initiation; tumorigenic

Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth most frequent cause of cancer related deaths in United States due to propensity to metastasis, invasion and resistance to chemotherapy. All stage 5-year survival rate is <5% with over 95% of the patients having recurrence of the tumor either locally or in the form of metastasis to other organs. Tumor relapse has been largely attributed to the presence of tumor initiating cells (TIC) or cancer stem cells (CSC). CSCs or TICs are quiescent cells within a tumor that are resistant to chemotherapy and are responsible for tumor recurrence. Thus therapies directed against TICs should lead to decreased tumor recurrence and metastases. Unfortunately, currently no chemotherapeutic agents are known to target TICs. CD133 is one of the surface markers that have been used in isolation and characterization of pancreatic tumor initiating cells. However, the biological role of CD133 is not known. Our group has recently evaluated Minnelide , a water soluble pro-drug of triptolide in pre-clinical studies on multiple animal models of pancreatic cancer with very promising results. However, the effect of Minnelide on prevention of tumor recurrence has not been studied in great detail. The current proposal is focused on elucidating the downstream events that are triggered by CD133 expression on a tumor initiating cell resulting in tumor recurrence and invasion leading to metastasis in this disease and evaluating the effect of Minnelide on this cell population.

胰腺导管腺癌（PDAC）是目前第四大最常见的癌症相关原因 在美国，由于转移倾向、侵袭和化疗耐药而死亡。全阶段 5年生存率<5%，超过95%的患者肿瘤局部或局部复发 转移至其他器官的形式。肿瘤复发很大程度上归因于肿瘤的存在 起始细胞（TIC）或癌症干细胞（CSC）。 CSC 或 TIC 是肿瘤内的静止细胞 对化疗有抵抗力并导致肿瘤复发。因此针对 TIC 的治疗 应导致减少肿瘤复发和转移。不幸的是，目前尚无化疗药物 已知药剂以 TIC 为目标。 CD133 是已用于分离和表征胰腺的表面标记物之一 肿瘤起始细胞。然而，CD133 的生物学作用尚不清楚。我们组最近评估了 Minnelide ，一种水溶性雷公藤内酯醇前药，在多种胰腺动物模型中进行临床前研究 癌症，具有非常有希望的结果。然而，明奈利特在预防肿瘤复发方面的作用尚未得到证实。 没有被详细研究过。当前提案的重点是阐明下游事件 由肿瘤起始细胞上的 CD133 表达触发，导致肿瘤复发和侵袭 导致这种疾病的转移并评估 Minnelide 对该细胞群的影响。