Abstract
Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating macrophages that are known to orchestrate many aspects of OS stromal signaling and disease progression. In particular, increased infiltration of M2-like tumor-associated macrophages (TAMs) has been associated with OS metastasis and poor patient prognosis despite currently used aggressive therapies regimens. This review aims to provide a summary update of current macrophage-centered knowledge and to discuss the possible roles that macrophages play in the process of OS metastasis development focusing on the potential influence of stromal cross-talk signaling between TAMs, cancer-stem cells and additional OSs tumoral microenvironment factors.
Highlights
Osteosarcoma (OS) is the most common type of malignant primary tumor in bone tissue, affecting mainly children and young adults
A major influential component within the tumor microenvironment (TME) are tumor-associated macrophages (TAMs) that are immune cells involved in inflammatory responses and tissue homeostasis [3]
A higher density of M2-type TAMs were found in lung metastases compared to primary OS in association with proinflammatory molecules resulting in increased tumor invasive capability [5]
Summary
Osteosarcoma (OS) is the most common type of malignant primary tumor in bone tissue, affecting mainly children and young adults. Research into the molecular cell signaling components involved in OS has led to an interest in evaluating potential therapeutic targets to block disease progression. A major influential component within the TME are tumor-associated macrophages (TAMs) that are immune cells involved in inflammatory responses and tissue homeostasis [3]. Additional studies demonstrated the participation of TAMs in promoting angiogenesis via the activation of intracellular signaling pathways known to be involved in cancer progression [6,7]. We aim to provide a current and comprehensive update about the known factors participating in the recruitment and activation of TAMs and the mechanism by which TAMs supports tumor metastasis in OS, focusing attention on the relationships between the signaling regulating the cross-talk between TAMs, cancer stem-cells (CSCs) and mesenchymal stem cells (MSCs) in primary and metastatic OS. Anticancer therapy based on macrophage-centered approaches have been investigated, a better understanding of the role of TAMs in OS is required to improve and develop therapeutic strategies targeting macrophages
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