A subpopulation of osteoblasts was identified in the bone tumor microenvironment in vivo of both humans and mice with bone metastatic breast cancer that express RUNX2/OCN/OPN but is negative for IL-6 and alpha-smooth muscle actin.
Importantly, JNK inhibition or disruption of SPP1 or TNC expression sensitizes experimental mammary tumors and metastases to chemotherapy, thus providing insights to consider for future treatment strategies against metastatic breast cancer.
In contrast, delivery of antimiR-218-5p decreased Wnt activity and the expression of metastasis-related genes, including bone sialoprotein (BSP/IBSP), osteopontin (OPN/SPP1) and CXCR-4, implicating a Wnt/miR-218-5p regulatory network in bone metastatic breast cancer.