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

乳腺癌的骨转移能力是亚型依赖的。此外，对乳腺癌转移的生物学和分子原理知之甚少，乳腺癌细胞如何修饰和利用骨中的造血干细胞和祖细胞生态位仍然是一个难以捉摸的问题。由于这一现象的潜在功能机制在很大程度上是未知的，我们计划分析BC细胞出现的质膜突起在迁移、粘附和侵袭骨髓微环境中的意义。将评估调节癌细胞转移能力的因子和/或信号通路的形态学影响。作为骨髓龛的细胞代表，间充质基质细胞（及其衍生的成骨细胞）将被使用。BC细胞和骨源性细胞之间的细胞间通讯机制也将被研究，并将特别关注可以作为隧道纳米管的薄膜过程。为了临床翻译，我们将研究这些质膜突起和通讯途径在药物反应、转移潜力和BC固有分子亚型方面的作用。

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.