Origin and Lineage of Differentiation of Kaposi's Sarcoma

卡波西肉瘤的起源和分化谱系

• 批准号: 8839925
• 负责人: Dirk P Dittmer
• 金额: $ 17.29万
• 依托单位: STELLENBOSCH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-13 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8839925
• 关键词: Acquired Immunodeficiency Syndrome; Address; Africa South of the Sahara; African; Antibodies; Biology; Biopsy; Blood Vessels; Case Series; Cell Line; Cell Lineage; Cells; Collaborations; Collection; Color; Country; Endothelial Cells; European; Fibroblasts; Freezing; Gene Expression; Genes; Genetic Transcription; Geography; HIV; Heart; Histocytochemistry; Histologic; Histopathology; Hospitals; Human Herpesvirus 8; Immune; Intervention; Kaposi Sarcoma; Kidney; Knowledge; Lasers; Learning; Lesion; Lymphatic Endothelial Cells; Lymphoma; Malawi; Malignant Neoplasms; Measures; Mesenchymal; Microscopy; Nature; Normal Cell; North Carolina; Organ; PECAM1 gene; Pathology; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Prevalence; Proteins; Publishing; Role; Series; South Africa; Sum; Testing; Time; Tissue Microarray; Tissues; UNC Lineberger Comprehensive Cancer Center; Universities; Vascular Endothelial Growth Factor Receptor-3; Veins; Viral; Viral Genes; Woman; Work; base; cell type; cytotoxic; epithelial to mesenchymal transition; human FRAP1 protein; macrophage; men; men who have sex with men; mortality; named group; neoplastic cell; novel; prevent; prospective; public health relevance; research study; targeted treatment; tumor

 DESCRIPTION (provided by applicant): Kaposi sarcoma (KS) is the leading cancer in HIV+ persons in the US and world-wide. In some countries in Sub-Saharan Africa it is the most common cancer in the country. Unlike in the US both HIV+ men and women present with KS in South Africa. Crucial aspects of the biology and pathology of the KS tumor cell remain unknown. This represents a gap in our knowledge that prevents tumor-targeted therapies. Knowing the exact lineage and origin of the KS tumor cell is essential if we were to develop novel KS-specific therapies. These interventions, be it drugs or cytotoxic antibodies, must selectively target KS tumor cells and not the normal cells lining blood vessels in essential organs such as heart or kidney. Recent work from many groups found evidence for multiple cell types in KS and for multiple cell types that support KSHV replication: lymphatic endothelial cells (LEC), transdifferentiated vein endothelial cells (VEC), perictyes, mesenchymal cells akin to epithelial-mesenchymal transition (EMT) and stromal fibroblasts. In sum, 20 years after the discovery of KSHV, we still do not know exactly which cells make up a KS lesions, what the spectrum of KS lesions is, and if they respond differently to therapy. This R21 application seeks to address some of these questions through the Construction and analysis of a South African KS tissue microarray.

 描述（由申请人提供）：卡波西肉瘤（KS）是美国和世界范围内HIV+人群的主要癌症。在撒哈拉以南非洲的一些国家，它是该国最常见的癌症。与美国不同，南非的艾滋病毒阳性男性和女性都患有KS。KS肿瘤细胞的生物学和病理学的关键方面仍然未知。这代表了我们在阻止肿瘤靶向治疗方面的知识差距。如果我们要开发新的KS特异性疗法，了解KS肿瘤细胞的确切谱系和起源是必不可少的。这些干预措施，无论是药物还是细胞毒性抗体，都必须选择性地靶向KS肿瘤细胞，而不是心脏或肾脏等重要器官中的正常血管细胞。许多研究小组最近的工作发现了KS中多种细胞类型和支持KSHV复制的多种细胞类型的证据：淋巴管内皮细胞（LEC），转分化的静脉内皮细胞（VEC），周膜，类似于上皮-间充质转化（EMT）的间充质细胞和基质成纤维细胞。总而言之，在发现KSHV 20年后，我们仍然不确切地知道哪些细胞构成KS病变，KS病变的谱是什么，以及它们是否对治疗有不同的反应。该R21申请试图通过构建和分析南非KS组织微阵列来解决这些问题中的一些。