Dissecting the role/s of breast cancer cell membrane protrusions in invasion, colonization and transformation of the bone marrow microenvironment: From cell biology to clinical applications

剖析乳腺癌细胞膜突起在骨髓微环境的侵袭、定植和转化中的作用：从细胞生物学到临床应用

• 批准号: 401114018
• 负责人: Dr. Denis Corbeil
• 金额: --
• 依托单位: Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/401114018?language=en
• 关键词: Dissecting; role; breast; cancer; cell

The bone metastasizing capacity of breast cancer (BC) is subtype dependent. Moreover, only little is known about the biology and molecular principles of BC metastasis and it remains elusive, how breast cancer cells modify and exploit the hematopoietic stem and progenitor cell niche in the bone. Since the underlying functional mechanisms of this phenomenon are largely unknown, we plan to dissect the implication of plasma membrane protrusions emerging from BC cells in migration, adhesion and invasion of bone marrow microenvironment. The morphological impact of factors and/or signaling pathways that modulate the metastatic capacity of cancer cells will be evaluated. As cellular representatives of bone marrow niches, mesenchymal stromal cells (and osteoblasts derived therefrom) will be used. Mechanisms of intercellular communication between BC cells and bone-derived cells will be investigated as well and a particular attention will be devoted to thin membrane processes that could act as tunneling nanotubes. For clinical translation, we will study the role of those plasma membrane protrusions and communication pathways with regard to drug response, metastatic potential and the intrinsic molecular subtypes of BC.

乳腺癌(BC)的骨转移能力具有亚型依赖性。此外，对BC转移的生物学和分子原理知之甚少，乳腺癌细胞如何修改和利用骨骼中的造血干细胞和祖细胞利基仍然难以捉摸。由于这种现象的潜在作用机制尚不清楚，我们计划剖析BC细胞产生的质膜突起在骨髓微环境迁移、黏附和侵袭中的作用。将对调节癌细胞转移能力的因素和/或信号通路的形态影响进行评估。作为骨髓壁龛的细胞代表，将使用间充质基质细胞(及其衍生的成骨细胞)。此外，还将研究BC细胞和骨源性细胞之间的细胞间通讯机制，并将特别关注可以作为隧道纳米管的薄膜过程。对于临床翻译，我们将研究这些质膜突起和通讯通路在药物反应、转移潜能和BC固有分子亚型中的作用。