Role of Tumor‐Associated Macrophages (TAM) in Cancer Related Inflammation

Sica, Antonio; Porta, Chiara

doi:10.1002/9780470669891.ch5

Cited by 67 publications

(86 citation statements)

References 119 publications

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“…24 ECMs sustained specific and organized localization of seeded monocytes, with CD68 + cells that were within the stroma of all ECMs, indicating accessibility of the stroma purified with this protocol. Second, infiltrated monocytes localized and distributed around dysplastic and neoplastic glands in the perilesional and CRCderived ECMs while they homogeneously distributed around the crypts of the healthy-derived ECM and this was dependent on the unique properties of the different ECMs.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

“…Given the important role of the inflammatory infiltrate in cancer-related inflammation, 24 we assessed the ability of ECM to sustain infiltration and localization of leukocytes. We seeded peripheral blood-derived monocytes onto matrices derived from healthy, perilesional area, and tumor-bearing colon mucosa, and we performed immunohistochemical staining with anti-CD68 antibody to identify monocytes in the healthy colon mucosa, perilesional area, and CRC.…”

Section: Scanning Electron Microscopymentioning

confidence: 99%

See 1 more Smart Citation

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

Genovese

Zawada

Tosoni

et al. 2014

Tissue Engineering Part A

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The interplay between tumor cells and the microenvironment has been recognized as one of the hallmarks of cancer biology. To assess the role of extracellular matrix (ECM) in the modulation of tissue homeostasis and tumorigenesis, we developed a protocol for the purification of tissue-derived ECM using mucosae from healthy human colon, perilesional area, and colorectal carcinoma (CRC). Matched specimens were collected from the left colon of patients undergoing CRC resection surgery. ECMs were obtained from tissues that were decellularized with hypotonic solutions containing ionic and nonionic detergents, hypertonic solution, and endonuclease in the absence of denaturing agents. Mucosae-derived ECMs maintained distribution and localization of proteins and glycoproteins typical of the original tissues, and showed different three-dimensional (3D) structures among normal versus perilesional and tumor-derived stroma. The three types of ECM differentially regulated the localization and organization of seeded monocytes and cancer cells that were located and organized as in the original tissue. Specifically, healthy, perilesional, and CRC-derived ECMs sustained differentiation and polarization of cancer epithelial cells. In addition, healthy, but not perilesional and CRC-derived ECM constrained invasion of cancer cells. All three ECMs sustained turnover between cell proliferation and death up to 40 days of culture, although each ECM showed different ability in supporting cell proliferation, with tumor > perilesional > healthy-derived ECMs. Healthy-, perilesional-and CRC-derived ECM differently modulated cell homeostasis, spreading in the stroma and turnover between proliferation and death, and equally supported differentiation and polarization of cancer epithelial cells, thus highlighting the contribution of different ECMs modulating some features of tissue homeostasis and tumorigenesis. Moreover, these ECMs provide competent scaffolds useful to assess efficacy of antitumor drugs in a 3D setting that more closely recapitulates the native microenvironment. Further, ECM-based scaffolds may also be beneficial for future studies seeking prognostic and diagnostic stromal markers and targets for antineoplastic drugs.

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Section: Conclusion and Discussionmentioning

confidence: 99%

Section: Scanning Electron Microscopymentioning

confidence: 99%

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

Genovese

Zawada

Tosoni

et al. 2014

Tissue Engineering Part A

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“…Tissue infiltration by macrophages is a dramatic and common feature of inflammation, angiogenesis and cancer (Pollard, 2004;Sica, 2010). High densities of tumor-infiltrating macrophages are associated with poor survival in patients with MM (Burt et al, 2011).…”

Section: Cross-talk Between Inflammation and Angiogenic Growth Factorsmentioning

confidence: 99%

“…In fact, the recruitment and infiltration of macrophages in the tumor microenvironment can activate them to support the malignant progression of cancer cells. These macrophages are called tumor-associated macrophages (TAMs) (Lawrence, 2011;Sica, 2010). Cancer cells cocultured with macrophages and incubated with inflammatory cytokines are synergistically stimulated to produce various angiogenesis-related factors (Izzi et al, 2009;Ono, 2008).…”

Section: Cross-talk Between Inflammation and Angiogenic Growth Factorsmentioning

confidence: 99%

Role of Inflammation and Angiogenic Growth Factors in Malignant Mesothelioma

Albonici¹,

Palumbo²,

Manzari³

2012

Malignant Mesothelioma

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“…Hypoxic conditions in tumors stimulate the expression of proangiogenic molecules by activating hypoxia-inducible factors (HIFs) in macrophages [19,[50][51][52][53][54][55][56][57][58]. Activated macrophages also release nitric oxide (NO), a molecule that provokes increased vascular flow [46,[59][60][61][62][63][64]. Myeloid derived suppressor cells (MDSC, see below) represent another cell population involved in tumor angiogenesis.…”

Section: Angiogenesis Hypoxia and Oxygen Regulationmentioning

confidence: 99%

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

Schwendener¹,

Mete²

2013

Frontiers in Clinical Drug Research - Anti-Cancer Agents

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Solid tumors grow within a complex microenvironment composed of diverse cell types such as fibroblasts, endothelial cells, mast cells, macrophages and immune cells that are attracted by tumor cell derived factors and embedded in an extracellular matrix. Molecular and cellular interactions between epithelial cells and cells surrounding the tumor stroma promote growth, invasion and spread of tumors. To delay or impede tumor growth, the tumor microenvironment (TME) is increasingly being explored as a potential therapeutic target for which novel strategies are developed. lt;/pgt;lt;pgt; This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed. This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed.

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Role of Tumor‐Associated Macrophages (TAM) in Cancer Related Inflammation

Cited by 67 publications

References 119 publications

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

Role of Inflammation and Angiogenic Growth Factors in Malignant Mesothelioma

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

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