Bone Metastatic Breast Cancer: Advances in Cell Signaling and Autophagy Related Mechanisms

Abstract

Bone metastasis is a frequent complication of breast cancer with nearly 70% of metastatic breast cancer patients developing bone metastasis during the course of their disease. The bone represents a dynamic microenvironment which provides a fertile soil for disseminated tumor cells, however, the mechanisms which regulate the interactions between a metastatic tumor and the bone microenvironment remain poorly understood. Recent studies indicate that during the metastatic process a bidirectional relationship between metastatic tumor cells and the bone microenvironment begins to develop. Metastatic cells display aberrant expression of genes typically reserved for skeletal development and alter the activity of resident cells within the bone microenvironment to promote tumor development, resulting in the severe bone loss. While transcriptional regulation of the metastatic process has been well established, recent findings from our and other research groups highlight the role of the autophagy and secretory pathways in interactions between resident and tumor cells during bone metastatic tumor growth. These reports show high levels of autophagy-related markers, regulatory factors of the autophagy pathway, and autophagy-mediated secretion of matrix metalloproteinases (MMP’s), receptor activator of nuclear factor kappa B ligand (RANKL), parathyroid hormone related protein (PTHrP), as well as WNT5A in bone metastatic breast cancer cells. In this review, we discuss the recently elucidated mechanisms and their crosstalk with signaling pathways, and potential therapeutic targets for bone metastatic disease.

Exploring the Mechanism of Traditional Chinese Medicine in Preventing Bone Metastasis of Breast Cancer through Data Mining

“…However, the molecular mechanism of bone metastasis of breast cancer has not been completely clari ed [33]. Currently, palliative treatment, including local treatment and systemic treatment, is commonly used for the treatment of breast bone metastases, which can prolong the quality of life and time of patients but cannot improve the survival rate of patients [34].…”

Proteomic analysis of spinal cord tissue in a rat model of cancer-induced bone pain

“…Nearly 70% of patients with metastatic breast cancer develop bone metastases. Bone metastasis causes osteolysis, spinal cord compression, and different degrees of pain ( Othman et al, 2021 ). In this study, a rat model of CIBP was established to investigate the mechanisms of cancer-induced bone pain.…”

Management of pain in patients with bone metastases

“…In fact, different tumors have different ways to change the balance of local bone metabolism. For example, breast cancer cells secrete parathyroid hormone related peptide (PTHrP) to activate osteoblasts to secrete RANKL and inhibit the expression of osteoprotegerin(OPG), which ultimately leads to increased osteoclast activity and the occurrence of bone FIGURE 1 metastasis (9). It is also worth noting that activation of bone absorption leads to the release of a large number of growth factors.…”