Elucidating Essential Components of Bone Marrow Metastasis

描述（由申请人提供）：在许多致命性癌症中观察到骨髓转移。肿瘤细胞优先迁移到骨腔作为骨髓组成的函数。我们已经开发了一种骨髓的组织工程类似物，并计划使用这种结构来识别骨髓转移小生境的关键基质细胞成分。我们建议：1）开发微流控平台以在体外捕获迁移的肿瘤细胞，2）在芯片上创建肿瘤-基质微环境，以及3）BMSC支架对肿瘤生长的体内比较和治疗研究。该项目将在K99培训期间为微流体，成像和癌症生物学的候选人提供必要的培训，并推动他成为生物材料和肿瘤学领域的成功独立研究者，作为研究型大学的R 00研究员。 公共卫生相关性： 肿瘤细胞转移是一种潜在的现象，导致90%的癌症相关死亡，骨髓已被认为是许多肿瘤的主要和早期转移部位。这项研究的目的是阐明骨髓小生境的基本基质成分，这些成分是使用工程化骨髓组织模型进行肿瘤转移的关键。这项研究的结果有望通过提供预防骨髓转移的替代治疗策略来直接改善公众健康。

DESCRIPTION (provided by applicant): Metastasis to the bone marrow is observed in a number of fatal cancers. Tumor cells preferentially migrate to the bone cavity as a function of composition of the bone marrow. We have developed a tissue engineered analogue of the bone marrow and plan to use this construct to identify the key stromal cellular components of a bone marrow metastatic niche. We propose to: 1) Develop a microfluidic platform to capture migratory tumor cells in vitro, 2) Create tumor-stroma microenvironments on-chip, and 3) In vivo comparison and treatment study of BMSC scaffolds on tumor growth. This project will provide essential training to candidate in microfluidics, imaging, and cancer biology during the K99 training period and propel him to be a successful independent investigator in the field of biomaterials and oncology as an R00 investigator at a research university. PUBLIC HEALTH RELEVANCE: Tumor cell metastasis is an insidious phenomenon that causes 90% of cancer-associated death and the bone marrow has been recognized as a prime and early metastatic site of numerous tumors. The objective of proposed research is to elucidate essential stromal components of bone marrow niche that are the linchpin of a tumor metastasis using engineered bone marrow tissue models. The results of this study are expected to directly improve public health by providing alternative therapeutic strategies for preventing bone marrow metastasis.