Abstract
Metastasis is the primary cause of mortality and morbidity in cancer patients. The bone marrow is a common destination for many malignant cancers, including breast carcinoma (BC), prostate carcinoma, multiple myeloma, lung carcinoma, uterine cancer, thyroid cancer, bladder cancer, and neuroblastoma. The molecular mechanism by which metastatic cancer are able to recognize, infiltrate, and colonize bone are still unclear. Chemokines are small soluble proteins which under normal physiological conditions mediate chemotactic trafficking of leukocytes to specific tissues in the body. In the context of metastasis, the best characterized role for the chemokine system is in the regulation of primary tumor growth, survival, invasion, and homing to specific secondary sites. However, there is ample evidence that metastatic tumors exploit chemokines to modulate the metastatic niche within bone which ultimately results in osteolytic bone disease. In this review, we examine the role of chemokines in metastatic tumor growth within bone. In particular, the chemokines CCL2, CCL3, IL-8/CXCL8, and CXCL12 are consistently involved in promoting osteoclastogenesis and tumor growth. We will also evaluate the suitability of chemokines as targets for chemotherapy with the use of neutralizing antibodies and chemokine receptor-specific antagonists.
Highlights
Cancer is the second leading cause of death in the developed world
We focus on the role of chemokines in directly influencing components of the bone microenvironment which in turn enable osteolysis and tumor growth
One study using AMD3100 showed that NSCLC metastatic colonization of bone did not require CXCR4 activity, outgrowth of metastases and subsequent osteolysis was dependent on the receptor [106]
Summary
Cancer is the second leading cause of death in the developed world. Metastatic spread of tumor cells to vital organs results in mortality and morbidity [1, 2]. The metastatic process is complex and involves genetic alterations of the cancer cells as well as interaction with the tumor microenvironment [3,4,5,6]. Each stage requires close collaboration of cancerous cells with specific elements of the microenvironment. Chemokines and Bone Metastasis that govern the spread of cancers to specific organs such as the bone remains unclear, technological advances have allowed examination of gene regulation in regards to organotropism. Such studies have found that tumor cells may acquire specific genetic phenotypes, with activation of specific cytokines and/or proteases which may govern metastasis to specific organs
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