Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2021 May 11;22(10):5078. doi: 10.3390/ijms22105078

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

Selected soluble and cellular inflammatory mediators of bone metastasis. Breast and prostate cancer are among the malignancies with the highest propensity to metastasize to bone (1). Cancer cells from the primary tumor undergo epithelial-to-mesenchymal transition (EMT) (2) and start to extravasate (3). Directly detached from the primary tumor or after metastasis to lymph nodes, circulating tumor cells (CTCs) metastasize to bone via the blood stream (4) which leads to seeding and colonization of single CTCs within the bone marrow (5). After a period of dormancy, disseminated tumor cells (DTCs) start to grow to full-blown metastases (5). Several cellular and soluble inflammatory factors maintain and drive the vicious cycle of bone metastases within the tumor microenvironment (6). The involved mechanisms are (i) induction of angiogenesis; (ii) mediation of tumor and immune cell recruitment and activation; (iii) maintenance of tumor cell growth and survival; (iv) tumor-promoting education of resident adipocytes, stromal cells, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAM); as well as the acceleration of osteoclastogenesis by inhibiting osteoblastogenesis and driving a local proinflammatory signature. CC-chemokine ligand 2 (CCL2); CC-chemokine ligand 5 (CCL5); C-X-C motif chemokine 1 (CXCL1); C-X-C motif chemokine 2 (CXCL2); C-X-C motif chemokine 12 (CXCL12); C-X-C Motif Chemokine Receptor 4 (CXCR4); cyclooxygenase-2 (COX-2); interleukin-1β (IL-1β); interleukin-6 (IL-6); interleukin-8 (IL-8); interleukin-11 (IL-11); macrophage colony-stimulating factor (M-CSF); matrix metalloproteinases (MMPs); osteoblasts (OBs); osteoclasts (OCs); osteoprotegerin (OPG); parathyroid hormone-related protein (PTHrP); receptor activator of NF-κB ligand (RANKL); transforming growth factor beta (TGF-β); tumor necrosis factor alpha (TNF-α); vascular endothelial growth factor (VEGF). Created with BioRender.com (accessed date 7 May 2021).