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: 9556631
• 负责人: Kandice Tanner
• 金额: $ 32.09万
• 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/9556631
• 关键词: Adherence; Biophysical Process; Blood capillaries; Cancer Patient; Cardiovascular system; Cells; Chemicals; Cutaneous Melanoma; Distant; Environment; Genetic; Immune; 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。播散的肿瘤细胞（DTC）离开原始肿瘤以启动转移级联。在循环系统的成功导航之后，这些DTC的子集然后经由远端部位处的毛细血管离开并浸润组织实质。这些DTC通过对粘附、重塑和增殖机制知之甚少的机制在新环境中定植。该提案的目的是揭示肿瘤细胞可以异位定植于与其原始组织在化学和物理上都不同的组织的机制。已经确定了控制癌症转移中的组织向性的遗传因素，但是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没有很好地理解。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。