Biology of breast cancer bone metastasis

Abstract

Breast carcinoma ranks among the most prevalent malignancies in women. Breast carcinoma frequently metastasizes to bone and approximately 70% of patients with breast cancer have bone metastases, which generally are osteolytic lesions. They cause major morbidity and mortality in patients; and the available treatment options are limited. Bone-specific homing and colonization of cancer cells are important and interesting features of metastasis. There are complex and multiple steps in the process of bone metastasis; and the elaborate interaction between breast carcinoma and bone involves various cytokines, growth factors and cellular signals, which results in a vicious cycle and promotes tumor cell accumulation and osteolysis. Recent advances in molecular biology have resulted in major breakthroughs in our understanding of the pathogenesis of bone metastasis in breast cancer, which is critical in preventing metastasis, designing novel and targeted treatments and prolonging survival in this devastating condition.

Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis

“…Bone is a rich source of growth factors, including transforming growth factor (TGF) α and β, insulin-like growth factors (IGFs), and fibroblast growth factors (FGFs), that are released as a consequence of osteoclastic bone resorption and can stimulate cancer cell survival and production of more osteolytic factors [3].…”

Osteosarcoma

“…Several researchers explore the tumor-environment interactions for the more common bone-metastasizing cancers such as breast and prostate adenocarcinoma. (74)(75)(76)(77)(78) It is unclear to what extent these same mechanisms are operative in osteosarcoma, which arises from as well as disseminates to bone. This remains a critical direction for future research efforts.…”

Membrane lipids in invadopodia and podosomes: Key structures for cancer invasion and metastasis

“…Osteoclasts derived from such mice cannot adhere and spread properly, and fail to give rise to mature sealing zones when attached to the bone. Bone metastases from breast cancer are typically osteolytic and cause destruction of the bone [70]. Breast cancer cells augment the activity of bone resorption via promoting the differentiation and podosome formation of osteoclasts by secreting transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), interleukins (ILs), and parathyroid hormone-related protein (PTHrP), which leads to osteolytic bone metastasis.…”