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，这是该国最常见的癌症。与美国不同的是，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。这代表了我们在阻碍肿瘤靶向治疗方面的知识空白。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至关重要。这些干预措施，无论是药物还是细胞毒性抗体，都必须选择性地针对 KS 肿瘤细胞，而不是心脏或肾脏等重要器官血管内壁的正常细胞。许多小组最近的工作发现了 KS 中多种细胞类型以及支持 KSHV 复制的多种细胞类型的证据：淋巴内皮细胞 (LEC)、转分化静脉内皮细胞 (VEC)、周细胞、类似于上皮间质转化 (EMT) 的间充质细胞和基质成纤维细胞。总之，在发现 KSHV 20 年后，我们仍然不知道到底哪些细胞构成了 KS 病变，KS 病变的范围是什么，以及它们对治疗的反应是否不同。该 R21 应用旨在通过构建和分析南非 KS 组织微阵列来解决其中一些问题。