Modulation of Cell Migration, Survival and Angiogenesis by KSHV

KSHV 对细胞迁移、存活和血管生成的调节

• 批准号: 8686761
• 负责人: BLOSSOM A DAMANIA
• 金额: $ 28.35万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 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/8686761
• 关键词: Acquired Immunodeficiency Syndrome; Adhesions; Affect; Apoptotic; Automobile Driving; Biological; Biology; CCL2 gene; CXCL1 gene; Cell Proliferation; Cell Survival; Cell physiology; Cells; Endothelial Cells; Future; Growth Factor; HIV Seropositivity; Human; Human Herpesvirus 8; Immigration; Individual; Infection; Interleukin-6; Kaposi Sarcoma; Lesion; Leukocytes; Life; Malignant Neoplasms; Mediating; Multicentric Angiofollicular Lymphoid Hyperplasia; Pathogenesis; Pathway interactions; Play; Proteins; Role; Satellite Viruses; Signal Pathway; UCHL1 gene; Ubiquitin; Ubiquitination; Up-Regulation; Vascular Cell Adhesion Molecule-1; Viral; Viral Proteins; angiogenesis; antiangiogenesis therapy; cell growth; cell motility; chemokine; cytokine; in vivo; insight; migration; pathogen; primary effusion lymphoma; reactivation from latency; tumor; tumorigenesis

Kaposi's sarcoma-associated virus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KS is a highly angiogenic tumor that is driven by KSHV-infected endothelial cells, and KS lesions express high levels of cytokines and angiogenic growth factors. We have found that latent KSHV infection dramatically alters angiogenesis, migration, and survival of endothelial cells. Latent KSHV infection of endothelial cells results in the upregulation of multiple cytokines and chemokines. We hypothesize that the upregulated cytokines and chemokines play important roles in driving angiogenesis and cell proliferation of KSHV-infected cells, and we propose to determine the mechanism by which these factors regulate cell growth, survival, and angiogenesis. We will also determine how KSHV infection affects cell migration. Finally, we have identified cellular and viral proteins that modulate the ubiquitin pathway. Hence, we propose to determine how these factors alter cellular ubiquitination pathways, to promote cell migration and survival of the infected cell. In summary, we propose to analyze the biological pathways that are altered upon KSHV infection of endothelial cells in order to understand the mechanism of KSHV-mediated oncogenesis. We hypothesize that the modulation of cell migration, angiogenesis and anti-apoptotic pathways by KSHV promotes tumorigenesis and contributes to the pathogenesis associated with KSHV infection. Thus, the proposed studies will provide significant and biologically relevant insights into KSHV biology, and will also identify new targets for future therapies against KSHV-associated cancers.

卡波西肉瘤相关病毒（KSHV）是卡波西肉瘤（KS）的病原体，原发性 渗出性淋巴瘤（PEL）和多中心Castleman病（MCD）。KS是一种高度血管生成的肿瘤， 是由KSHV感染的内皮细胞驱动的，KS病变表达高水平的细胞因子和血管生成因子。 生长因子 我们发现潜伏性KSHV感染显著改变了血管生成、迁移和存活。 内皮细胞KSHV潜伏性感染内皮细胞导致多种细胞因子的上调 和趋化因子。我们推测上调的细胞因子和趋化因子在 驱动KSHV感染细胞的血管生成和细胞增殖，我们建议确定 这些因子调节细胞生长、存活和血管生成的机制。我们还将确定 KSHV感染如何影响细胞迁移最后，我们已经确定了细胞和病毒蛋白， 调节泛素途径。因此，我们建议确定这些因素是如何改变细胞 泛素化途径，以促进细胞迁移和受感染细胞的存活。总之，我们建议 分析KSHV感染内皮细胞后改变的生物学途径， 了解KSHV介导的肿瘤发生机制。我们假设细胞的调节 KSHV的迁移、血管生成和抗凋亡途径促进肿瘤发生， 与KSHV感染相关的发病机制。因此，拟议的研究将提供重要和 生物学相关的见解KSHV生物学，也将确定新的目标，为未来的治疗， KSHV相关癌症。