Distant Relations: Macrophage Functions in the Metastatic Niche

Doak, Geneva R.; Schwertfeger, Kathryn L.; Wood, David E.

doi:10.1016/j.trecan.2018.03.011

Cited by 89 publications

(86 citation statements)

References 69 publications

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“…The interaction between cancer cells and myeloid cells has also been implicated in cancer progression. For instance, inflammatory monocytes with Ly6C expression can facilitate the extravasation of cancer cells in the lung by secreting chemokine C-C-motif ligand 2 (CCL2) 55 and vascular endothelial growth factor 56 . Then, macrophages bind to cancer cells and increase the survival of cancer cells.…”

Section: Chronic Inflammation Awakens Dormant Cellsmentioning

confidence: 99%

The force awakens: metastatic dormant cancer cells

2020

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Recurrent cancer that spreads to distant sites is the leading cause of disease-related death among cancer patients. Cancer cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. These dormant cancer cells (DCCs) are rarely detectable with current diagnostic systems. Moreover, they can interpret homoeostatic signals from the microenvironment, thereby evading immune surveillance and chemotherapy. Eventually, DCCs can reawaken in response to signals, which are not yet fully understood, resulting in recurrence and metastasis. Therefore, understanding the biology of DCC reawakening is key to preventing metastasis. Over the last decade, a growing body of literature has revealed the mechanisms involved in cancer dormancy and reawakening. The cytotoxic activity of immune cells can cause cancer cells to enter a dormant state, and chronic inflammation can reactivate cancer proliferation at distant sites. Upon the binding of circulating DCCs to extracellular molecules, various signaling cascades are activated and reinitiate cell proliferation. In the present review, we attempt to consolidate the existing literature to provide a framework for the understanding of this crucial step in cancer progression.

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Section: Chronic Inflammation Awakens Dormant Cellsmentioning

confidence: 99%

The force awakens: metastatic dormant cancer cells

2020

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“…Metastatic cancer cells need to evade the immune system, survive in the blood circulation, and reach distant sites to grow in different types of environments. The presence of TAMs in the primary tumor contributes to the progression of metastatic processes [91]. In addition, recent studies have identified a different population of macrophages in metastatic tissues, termed metastasis-associated macrophages (MAMs) [29,92].…”

Section: Role Of Metastasis-associated Macrophages In Metastatic Progmentioning

confidence: 99%

“…The recruitment of bone marrow-derived macrophages (BMDMs) promotes a pro-inflammatory environment in the metastatic niche to allow metastatic cancer cell establishment, support of tumor growth, and further recruitment of BMDMs, which sustain the formation of metastatic tumors [93]. In addition, it has been shown that MAMs derived from BMDMs support circulating cancer cell adhesion and migration to the metastatic niche by interactions between MAMs and cancer-associated fibroblasts (CAFs) or endothelial cells [91]. The bone marrow is rich in resident macrophages; hence, the bone tissue is a favorable microenvironment for the conditioning and formation of the metastatic niche where BMDMs may contribute enormously to the enrichment of the pro-tumorigenic MAM population in bone.…”

Section: Role Of Metastasis-associated Macrophages In Metastatic Progmentioning

confidence: 99%

Contribution of Macrophages and T Cells in Skeletal Metastasis

Mendoza-Reinoso

McCauley

Fournier

2020

Cancers

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Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in this review as they represent a great promise for patients suffering from incurable bone metastases.

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“…While many studies have demonstrated the role of TAMs in tumor progression in the primary tumor, less is known about the macrophages present at the metastatic site, metastasis-associated macrophages (MAMs), which promote later stages of metastasis. MAMs appear to promote metastatic tumor development in a manner similar to TAMs by initiating angiogenesis, inhibiting anti-tumor immune responses, and promoting matrix remodeling making MAMs potential targets for novel therapeutic intervention to inhibit metastatic development [17].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological prevention of surgery-accelerated metastasis in an animal model of osteosarcoma

et al. 2020

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Background: Osteosarcoma is a highly metastatic primary bone tumor that predominantly affects adolescents and young adults. A mainstay of treatment in osteosarcoma is removal of the primary tumor. However, surgical excision itself has been implicated in promoting tumor growth and metastasis, an effect known as surgery-accelerated metastasis. The underlying mechanisms contributing to surgery-accelerated metastasis remain poorly understood, but pro-tumorigenic alterations in macrophage function have been implicated. Methods: The K7M2-BALB/c syngeneic murine model of osteosarcoma was used to study the effect of surgery on metastasis, macrophage phenotype, and overall survival. Pharmacological prevention of surgery-accelerated metastasis was examined utilizing gefitinib, a receptor interacting protein kinase 2 inhibitor previously shown to promote anti-tumor macrophage phenotype. Results: Surgical excision of the primary tumor resulted in increases in lung metastatic surface nodules, overall metastatic burden and number of micrometastatic foci. This post-surgical metastatic enhancement was associated with a shift in macrophage phenotype within the lung to a more pro-tumor state. Treatment with gefitinib prevented tumorsupportive alterations in macrophage phenotype and resulted in reduced metastasis. Removal of the primary tumor coupled with gefitinib treatment resulted in enhanced median and overall survival. Conclusions: Surgery-accelerated metastasis is mediated in part through tumor supportive alterations in macrophage phenotype. Targeted pharmacologic therapies that prevent pro-tumor changes in macrophage phenotype could be utilized perioperatively to mitigate surgery-accelerated metastasis and improve the therapeutic benefits of surgery.

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Distant Relations: Macrophage Functions in the Metastatic Niche

Cited by 89 publications

References 69 publications

The force awakens: metastatic dormant cancer cells

The force awakens: metastatic dormant cancer cells

Contribution of Macrophages and T Cells in Skeletal Metastasis

Pharmacological prevention of surgery-accelerated metastasis in an animal model of osteosarcoma

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