The role of the tumor biofilm in determining tissue tropism

肿瘤生物膜在确定组织向性中的作用

• 批准号: 8938195
• 负责人: Kandice Tanner
• 金额: $ 32.35万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/8938195
• 关键词: Adherence; Biophysical Process; Blood capillaries; Cancer Patient; Cardiovascular system; Cells; Cutaneous Melanoma; Distant; Environment; Genetic; Immune; Left; Melanoma Cell; Microbial Biofilms; Neoplasm Metastasis; Organ; Role; Site; Tissues; capillary; environmental change; malignant breast neoplasm; mortality; neoplastic cell; tissue tropism; tumor

Metastasis remains a leading cause of mortality for cancer patients. Disseminated tumor cells (DTCs) leave the original tumor to initiate the metastatic cascade. After successful navigation of the circulatory system, a subset of these DTCs then exits via capillaries at a distant site and infiltrate the tissue parenchyma. These DTCs colonize this new environment by poorly understood mechanisms involving adherence, remodeling, and proliferation. The objective of this proposal is to uncover the mechanisms by which a tumor cell can ectopically colonize a tissue that is both chemically and physically different from its original tissue. The genetic factors governing tissue tropism in cancer metastasis have been identified but the contributions of the dynamic interactions between tumor cells, and the microenvironment of the metastasizing cells are not well understood. Here we aim to understand the biophysical mechanisms by which these environmental changes occur, and whether such changes can be reversed or blocked.

转移仍然是癌症患者死亡的主要原因。播散性肿瘤细胞(DTC)离开原始肿瘤，启动转移级联反应。在循环系统成功导航后，这些DTC的一部分随后通过远处的毛细血管退出，并渗入组织实质。这些树突状细胞通过涉及黏附、重塑和增殖的鲜为人知的机制在这个新环境中定居。这项提议的目的是揭示肿瘤细胞在化学和物理上与其原始组织不同的组织异位定植的机制。控制肿瘤转移的组织趋向性的遗传因素已经被确定，但肿瘤细胞之间的动态相互作用和转移细胞的微环境的贡献还不是很清楚。在这里，我们的目标是了解这些环境变化发生的生物物理机制，以及这些变化是否可以逆转或阻止。