Comparison of gene expression profile between primary and bone metastasized cancers

Bone metastasis occurs frequently in cancer patients. Conventional therapies have limited therapeutic outcomes, and thus, exploring the mechanisms of cancer progression in the bone metastasis is important to develop new effective therapies. In the bone microenvironment, adipocytes are the major stromal cells that interact with cancer cells during the bone metastasis. However, the comprehensive functions of bone marrow adipocytes in cancer progression are not yet fully understood. To address this, we investigated the role of bone marrow adipocytes on cancer cells, by focusing on an invasive front which reflects the direct effects of stromal cells on caner. In comprehensive histopathological and genetic analysis using bone metastasis specimens, we examined invasive fronts in bone metastasis and compared invasive fronts with adipocyte-rich bone marrow (adipo-BM) to those with hematopoietic cell-rich bone marrow (hemato-BM) as a normal counterpart of adipocytes. We found morphological complexity of invasive front with adipo-BM was significantly higher than that with hemato-BM. Based on immunohistochemistry, the invasive front with adipo-BM comparatively had significantly increased cancer-associated fibroblasts (CAFs) marker-positive area and lower density of CD8 positive lymphocytes compared to that with hemato-BM. RNA-seq analysis of primary and bone metastasis cancer reveals that bone metastasized cancer cells acquired drug resistance related gene expression phenotypes. Clearly, these findings indicate that bone marrow adipocytes provide favorable tumor microenvironment for cancer invasion and therapeutic resistance of bone metastasized cancers via CAF induction and immune evasion, providing a potential target for the treatment of bone metastasis. Six samples of primary cancer tissues (group 1) and six samples of bone metastasized cancer tissues from same patients of group 1 (group 2) were used. We compared gene expression pattern between group 1 and group 2. *** Raw data not provided due to Japan's personal information protection law. ***