The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone

Abstract

Tumor metastasis to bone is a common event in multiple forms of malignancy. Inflammation holds essential functions in homeostasis as a defense mechanism against infections and is a strategy to repair injured tissue and to adapt to stress conditions. However, exaggerated and/or persistent (chronic) inflammation may eventually become maladaptive and evoke diseases such as autoimmunity, diabetes, inflammatory tissue damage, fibrosis, and cancer. In fact, inflammation is now considered a hallmark of malignancy with prognostic relevance. Emerging studies have revealed a central involvement of inflammation in several steps of the metastatic cascade of bone-homing tumor cells through supporting their survival, migration, invasion, and growth. The mechanisms by which inflammation favors these steps involve activation of epithelial-to-mesenchymal transition (EMT), chemokine-mediated homing of tumor cells, local activation of osteoclastogenesis, and a positive feedback amplification of the protumorigenic inflammation loop between tumor and resident cells. In this review, we summarize established and evolving concepts of inflammation-driven tumorigenesis, with a special focus on bone metastasis.

Multiple pathogens and prostate cancer

“…Multiple pathogens are frequently present in prostate tissues and chronic exposure can lead to chronic inflammation and ultimately to prostate cancer. The relevant evidence has been reviewed in detail by De Bono et al [ 147 ] and Gobel et al [ 148 ].…”

The Breast Tumor Microenvironment: A Key Player in Metastatic Spread

“…As a result, the bone marrow sinusoids are more permissive to circulating tumor cells compared to other types of capillaries [ 113 ]. In addition, bone matrix cells such as osteoblasts secrete chemoattractants such as CXCL12, osteopontin, receptor activator of nuclear factor kappa-Β ligand (RANKL), and bone morphogenetic proteins (BMPs) that recruit cancer cells to the bone marrow [ 114 , 115 , 116 ]. Following their exit from the blood vessels into the bone marrow, cancer cells can then “hijack” osteoblast activity to promote osteoclastogenesis, increasing bone resorption [ 19 ].…”

Metagenomics studies for the diagnosis and treatment of prostate cancer

“…Ho et al 83 Schistosoma haematobium Oncogenic Parasite Urinary bladder cancer Santos et al 84 Clonorchis sinensis Cholangiocarcinoma Pakharukova et al 85 Opisthorchis viverrini Crellen et al 86 regions of the body, causing metastasis. [106][107][108] Inflammation may interfere with Natural Killer (NK) cells that mediate immune surveillance mechanisms. The tissue damage and regeneration caused by infection lead to an elevated amount of reactive nitrogen and oxygen species (RNS and ROS) which are responsible for cancer development as well as high DNA damage.…”

“…In addition, activation of fibroblast growth factor (FGF) and transforming growth factor‐beta (TGF‐β) are the results of chronic inflammation. Soluble inflammatory mediators released into the extracellular matrix (ECM) promote the formation of reactive stroma, resulting in the disruption of ECM; consequently, anoikis‐resistant (AR) cells 105 migrate to other regions of the body, causing metastasis 106–108 . Inflammation may interfere with Natural Killer (NK) cells that mediate immune surveillance mechanisms.…”