Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

Abstract

The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidence that when osteoblasts come into contact with disseminated breast cancer cells, the osteoblasts produce factors that initially reduce breast cancer cell proliferation, yet promote cancer cell survival in bone. Other laboratories have demonstrated that osteoblasts both directly and indirectly contribute to dormant cancer cell reactivation in bone. Moreover, we have demonstrated that osteoblasts undergo an inflammatory stress response in late stages of breast cancer, and produce inflammatory cytokines that are maintenance and survival factors for breast cancer cells and osteoclasts. Advances in understanding interactions between osteoblasts, osteoclasts, and bone metastatic cancer cells will aid in controlling and ultimately preventing cancer cell metastasis to bone.

How Prostate Cancer Cells Use Strategy Instead of Brute Force to Achieve Metastasis

“…In addition, PCa-derived EVs have been reported to play a role in metastatic bone remodeling including favoring the differentiation of osteoblasts, impairing the differentiation of osteoclasts, and driving osteomimicry of PCa cells in the bone microenvironment [43][44][45][46][47][48]. Intriguingly, integrins that are found in the exosomal cargo can be instrumental in organ-specific metastasis [49] and the transfer of αVβ6 integrins between PCa cells was shown to promote cell adhesion and migration [50].…”

STUDI AWAL ESTIMASI DOSIS INTERNAL 99mTc-MDP HASIL PRODUKSI PSTNT-BATAN PADA MANUSIA UNTUK DETEKSI METASTASIS DAN INFLAMASI TULANG BERBASIS UJI BIODISTRIBUSI HEWAN MODEL MENCIT

“…Sel osteogenik di permukaan luar akan membelah menjadi sel osteoblas (sel pembentukan tulang) sedangkan di dalam akan membentuk sel osteoklas (sel absorpsi dan degredasi tulang). Sel osteogenik berinteraksi dengan sel kanker berhubungan dalam penurunan aktivitas osteoblas dan peningkatan aktivitas osteoklas dan memicu proliferasi sel kanker [25]. Distribusi dosis yang diperoleh merupakan dosis efektif dari masing-masing organ yang dapat berasal dari organ itu sendiri ataupun berasal dari organ terdekat lainnya.…”

β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells

“…Primary osteoblasts or MC3T3E1 osteoblasts were grown to 90% confluence in 24-well tissue culture plates. In co-culture transwell assays, PC-3 and DU145 cells were cultured with serum-free DMEM/F-12 and DMEM, respectively, and MC3T3 E1 cells and primary osteoblasts were cultured with DMEM/F- 12…”

“…Prostate cancer is a cancer type that frequently metastasizes to bone and preferentially colonizes to osteoblast-rich area in early stages [12]. Activation of sympathetic nervous system modulated the bone marrow microenvironment, building a receptive niche for metastatic colonization of breast cancer cells [10].…”