Identifying host factors that block engraftment and progression of transmissible cancer as a model of AML

识别阻止传染性癌症植入和进展的宿主因素作为 AML 模型

• 批准号: 10367317
• 负责人: Michael Jeffrey Metzger
• 金额: $ 40.76万
• 依托单位: PACIFIC NORTHWEST RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367317
• 关键词: Acute Myelocytic Leukemia; Alleles; Animal Model; Animals; Biological Models; Bivalvia; Blood Circulation; Cancer Control; Cancer Model; Cancer Survivor; Cells; Cessation of life; Clams; Clinical; DNA; Data; Disease; Disease remission; Disseminated Malignant Neoplasm; Distant; Engraftment; Environment; Exposure to; Gene Expression; Gene Expression Profile; Genes; Genomic DNA; Genomic Segment; Granulocytic Sarcoma; Growth; Hemocytes; Host resistance; Human; Immune response; Injections; Integration Host Factors; Kinetics; Lead; Leukemic Cell; Liquid substance; Location; Maine; Malignant Neoplasms; Measures; Methods; Modeling; Nature; Neoplasm Metastasis; Neoplasms; Pathway interactions; Pattern; Population; Predisposition; Reporting; Resistance; Resistance to infection; Route; Sampling; Site; Solid; System; Testing; Time; Tissues; Translating; Travel; Water; base; blocking factor; cancer cell; cancer regression; cancer therapy; novel therapeutic intervention; pressure; prevent; public health relevance; response; transcriptomics; treatment strategy; tumor; tumor microenvironment; tumor progression

SUMMARY: Identification of host genes and pathways that can block cancer cell engraftment and growth could lead to revolutionary new cancer treatment strategies. In metastatic cancer, there are many steps in which cancer cells interact with the host microenvironment: the release of cells from their original location, travel through the circulation, engraftment into a distant location, and growth in the new environment. So-called liquid tumors like acute myeloid leukemia (AML) are not often considered to be metastatic, but leukemic cells disseminate throughout the body and can lead to solid metastasis-like tumors called myeloid sarcomas, interacting with the host microenvironment in similar ways. In the soft-shell clam (Mya arenaria), and other bivalves, fatal AML-like cancer lineages have evolved that metastasize repeatedly—not just from a primary to a secondary site, but from one whole animal to another, over and over again throughout the population for decades or longer. These fatal contagious cancers exert a strong selective pressure in nature to select for clams which can block engraftment and growth of this lineage of cancer cells. We will use this unique bivalve transmissible neoplasia (BTN) system as a model of AML to determine (1) which microenvironments expression patterns correlate with metastatic growth, (2) what genes correlate with resistance to progression, and (3) how different populations have evolved resistance to cancer. This study has the potential to provide an unprecedented understanding of cancer microenvironment and reveal new and important interactions between cancers and their hosts.

概括： 鉴定可以阻止癌细胞植入和生长的宿主基因和途径可能会导致 革命性的新癌症治疗策略在转移性癌症中，癌细胞有许多步骤。 与宿主微环境相互作用：细胞从原来的位置释放，穿过宿主微环境 循环，植入远处位置，并在新环境中生长。 像急性髓性白血病（AML）一样，通常不被认为是转移性的，但白血病细胞会播散 遍及全身，并可导致称为髓系肉瘤的实体转移样肿瘤，与 在软壳蛤（Mya arenararia）和其他双壳类动物中，以类似的方式对宿主微环境产生致命的影响。 类似 AML 的癌症谱系已经进化出反复转移——不仅仅是从原发性转移到继发性转移 地点，但从一个完整的动物到另一个，在整个种群中一遍又一遍地进行了数十年或 这些致命的传染性癌症本质上会产生强大的选择压力，以选择可以生存的蛤。 我们将使用这种独特的双壳类传染性癌细胞的植入和生长。 瘤形成 (BTN) 系统作为 AML 模型来确定 (1) 哪些微环境表达模式 与转移生长相关，(2) 哪些基因与进展抵抗相关，以及 (3) 如何相关 不同人群已经进化出了对癌症的抵抗力。这项研究有可能提供一种新的方法。 对癌症微环境的前所未有的了解并揭示新的重要相互作用 癌症与其宿主之间。