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

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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.