Tumor Microenvironment in Osteoblastic Bone Metastases: The Roles of NRP1 and NRP2

Bone marrow metastases are a major complication of advanced solid tumors, particularly prostate and breast cancers, and are frequently associated with osteoblastic changes in the local tumor microenvironment.

Neuropilin-2 (NRP2) is a transmembrane co-receptor involved in tumor progression, cellular plasticity, and angiogenesis. It also functions as a scaffolding receptor in the regulation of bone homeostasis and osteolineage differentiation. In addition, NRP2 has been implicated in the osteosclerotic differentiation of mesenchymal stromal cells in primary myelofibrosis and other hematologic neoplasms.

The aim of this project is to investigate the roles of NRP1 and NRP2 in the tumor microenvironment of bone marrow metastatic lesions. We will identify NRP1- and NRP2-positive stromal cell populations in human bone marrow trephine biopsies and analyze their spatial and cellular interactions with tumor cells, immune cells, and other stromal components. This work will contribute to a better understanding of the mechanisms underlying osteoblastic bone metastasis and may help identify potential cellular and molecular therapeutic targets.