CXCR2-Dependent Pancreatic Cancer Progression and Metastasis

CXCR2依赖性胰腺癌进展和转移

• 批准号: 8883410
• 负责人: RAKESH K SINGH
• 金额: $ 17.9万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8883410
• 关键词: Animal Model; Area; Automobile Driving; Autopsy; Bone Marrow; CXC Chemokines; Cancer Etiology; Cancer Model; Cancer Patient; Cells; Cessation of life; Chronic; Data; Development; Diagnosis; Diagnostic Neoplasm Staging; Endothelial Cells; Environment; Epithelial Cells; G-Protein-Coupled Receptors; Goals; Human; IL8RB gene; Infiltration; Inflammation; Inflammatory; Leukocytes; Ligands; Link; Maintenance; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Modeling; Molecular Biology; Myelogenous; Neoplasm Metastasis; Patients; Phenotype; Play; Primary Neoplasm; Proteins; Publishing; Recruitment Activity; Reporting; Role; Signal Transduction; Specimen; Staging; Survival Rate; Testing; Tissues; Transplantation; Treatment outcome; Tumor stage; Woman; advanced disease; angiogenesis; beta-Chemokines; cancer cell; cell behavior; chemokine; cytokine; density; improved; insight; men; neoplastic cell; novel strategies; pancreatic cancer cells; pancreatic neoplasm; pancreatic tumorigenesis; progenitor; programs; receptor; therapeutic target; tumor; tumor growth; tumor microenvironment; tumor progression; tumorigenesis; tumorigenic

Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women and it is one ofthe most lethal malignancies with a 5-year survival rate of <5% and median survival duration of less than 6 months. In recent years there have been important advances in the understanding of the molecular biology of pancreatic cancer as well as in diagnosis, staging and treatment in patients with eariy stage tumor. However, minimal progress has been made in our understanding in progression and metastasis and treatment in patients with advanced disease. Recent reports and our preliminary data suggest that inflammation, tumorigenesis, and progression to metastasis are intimately linked in pancreatic cancer. Chronic inflammation can drive tumorigenesis, and tumors are inherently pro-inflammatory with infiltrating leukocytes thought critical for tumor maintenance and progression. Thus, molecules driving tumor-associated inflammation have considerable potential as therapeutic targets, yet this area remains relatively under-explored in pancreatic cancer. Chemokines are secreted proteins that regulate cell behavior via G-protein coupled receptors. Subsets of CC and CXC chemokines orchestrate tissue inflammation by recruiting and activating leukocytes and by regulating endothelial and epithelial cells. Constitutive expression of pro-inflammatory chemokines, a hallmark of many human cancers, helps establish a supportive tumor stroma and in some cases, directly stimulates tumor proliferation and invasion via receptors on tumor cells. Evidence suggests that CXCR2 regulates leukocytes, endothelial cells (ECs), and/or tumor cells and their precursors. To our knowledge, very little is known about the role of CXCR2 in de novo pancreatic cancer progression and metastasis.

胰腺癌是男性和女性癌症相关死亡的第四大原因， 最致命的恶性肿瘤之一，5年生存率<5%，中位生存期小于 6个月近年来，对肿瘤分子生物学的理解取得了重要进展 对胰腺癌的诊断、分期和早期肿瘤患者的治疗具有重要意义。然而，在这方面， 我们对肿瘤进展、转移和治疗的理解进展甚微 患有晚期疾病最近的报告和我们的初步数据表明，炎症，肿瘤发生， 进展到转移与胰腺癌密切相关。慢性炎症可以驱动 肿瘤是固有的促炎性的，浸润的白细胞被认为是肿瘤发生的关键。 保持和进步。因此，驱动肿瘤相关炎症的分子具有相当大的 作为治疗靶点的潜力，但这一领域在胰腺癌中仍然相对不足。 趋化因子是通过G蛋白偶联受体调节细胞行为的分泌蛋白。的子集 CC和CXC趋化因子通过募集和激活白细胞以及通过激活白细胞来协调组织炎症。 调节内皮细胞和上皮细胞。促炎趋化因子的组成型表达， 许多人类癌症有助于建立支持性肿瘤基质，在某些情况下直接刺激肿瘤 通过肿瘤细胞上的受体增殖和侵袭。有证据表明CXCR 2调节白细胞， 内皮细胞（EC）和/或肿瘤细胞及其前体。据我们所知，对这一点知之甚少。 CXCR 2在原发性胰腺癌进展和转移中的作用。