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The role IL-1 in tumor-mediated angiogenesis.

Voronov E, Carmi Y, Apte RN - Front Physiol (2014)

Bottom Line: IL-1 initiates and propagates inflammation, mainly by inducing a local cytokine network and enhancing inflammatory cell infiltration to affected sites and by augmenting adhesion molecule expression on ECs and leukocytes.In this review, we summarize the interactions between IL-1 and other pro-angiogenic factors during normal and pathological conditions.In addition, the feasibility of IL-1 neutralization approaches for anti-cancer therapy is discussed.

View Article: PubMed Central - PubMed

Affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev Beer-Sheva, Israel.

ABSTRACT
Tumor angiogenesis is one of the hallmarks of tumor progression and is essential for invasiveness and metastasis. Myeloid inflammatory cells, such as immature myeloid precursor cells, also termed myeloid-derived suppressor cells (MDSCs), neutrophils, and monocytes/macrophages, are recruited to the tumor microenvironment by factors released by the malignant cells that are subsequently "educated" in situ to acquire a pro-invasive, pro-angiogenic, and immunosuppressive phenotype. The proximity of myeloid cells to endothelial cells (ECs) lining blood vessels suggests that they play an important role in the angiogenic response, possibly by secreting a network of cytokines/chemokines and inflammatory mediators, as well as via activation of ECs for proliferation and secretion of pro-angiogenic factors. Interleukin-1 (IL-1) is an "alarm," upstream, pro-inflammatory cytokine that is generated primarily by myeloid cells. IL-1 initiates and propagates inflammation, mainly by inducing a local cytokine network and enhancing inflammatory cell infiltration to affected sites and by augmenting adhesion molecule expression on ECs and leukocytes. Pro-inflammatory mediators were recently shown to play an important role in tumor-mediated angiogenesis and blocking their function may suppress tumor progression. In this review, we summarize the interactions between IL-1 and other pro-angiogenic factors during normal and pathological conditions. In addition, the feasibility of IL-1 neutralization approaches for anti-cancer therapy is discussed.

No MeSH data available.


Related in: MedlinePlus

Crosstalk between IL-1β and VEGF in the tumor microenvironment. (A) In the tumor microenvironment, IL-1β can be expressed initially by the malignant cells. In turn, IL-1β can recruit myeloid cells from the BM and further activate them to secrete pro-inflammatory and pro-angiogenic molecules, such as VEGF and IL-1β. Furthermore, IL-1β keeps myeloid cells in their immature stage, where they are pro-invasive and immunosuppressive. IL-1β can also activate tissue-resident ECs to produce VEGF and other pro-angiogenic factors. The malignant cells can also be activated by IL-1β for increased invasiveness. VEGF in the tumor microenvironment activates ECs and myeloid cells and also has homeostatic effects on these cells. (B) In the absence of IL-1β, inflammation, as well as VEGF production is diminished, which results in reduced invasiveness. Lack of IL-1β in the tumor microenvironment also induces the maturation of MDSCs into anti-tumor M1 macrophages.
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Figure 1: Crosstalk between IL-1β and VEGF in the tumor microenvironment. (A) In the tumor microenvironment, IL-1β can be expressed initially by the malignant cells. In turn, IL-1β can recruit myeloid cells from the BM and further activate them to secrete pro-inflammatory and pro-angiogenic molecules, such as VEGF and IL-1β. Furthermore, IL-1β keeps myeloid cells in their immature stage, where they are pro-invasive and immunosuppressive. IL-1β can also activate tissue-resident ECs to produce VEGF and other pro-angiogenic factors. The malignant cells can also be activated by IL-1β for increased invasiveness. VEGF in the tumor microenvironment activates ECs and myeloid cells and also has homeostatic effects on these cells. (B) In the absence of IL-1β, inflammation, as well as VEGF production is diminished, which results in reduced invasiveness. Lack of IL-1β in the tumor microenvironment also induces the maturation of MDSCs into anti-tumor M1 macrophages.

Mentions: Finally, this review demonstrated the important role of the IL-1 family molecules, especially IL-1β, in the tumor microenvironment. IL-1β represents a major upstream cytokine that controls the local pro-inflammatory cascade and thereby affects the balance between protective immunity and destructive inflammation. IL-1 modulates diverse cells in the tumor microenvironment and acts together with VEGF in mounting and maintaining tumor-mediated angiogenesis (Figure 1). Thus, its neutralization should reduce tumor progression and invasiveness via its affect on pro-tumorigenic cells, and on the tumor-induced angiogenic switch. Further characterization of the optimal conditions for IL-1 neutralization could lead to the application of anti-IL-1 approaches in cancer therapy.


The role IL-1 in tumor-mediated angiogenesis.

Voronov E, Carmi Y, Apte RN - Front Physiol (2014)

Crosstalk between IL-1β and VEGF in the tumor microenvironment. (A) In the tumor microenvironment, IL-1β can be expressed initially by the malignant cells. In turn, IL-1β can recruit myeloid cells from the BM and further activate them to secrete pro-inflammatory and pro-angiogenic molecules, such as VEGF and IL-1β. Furthermore, IL-1β keeps myeloid cells in their immature stage, where they are pro-invasive and immunosuppressive. IL-1β can also activate tissue-resident ECs to produce VEGF and other pro-angiogenic factors. The malignant cells can also be activated by IL-1β for increased invasiveness. VEGF in the tumor microenvironment activates ECs and myeloid cells and also has homeostatic effects on these cells. (B) In the absence of IL-1β, inflammation, as well as VEGF production is diminished, which results in reduced invasiveness. Lack of IL-1β in the tumor microenvironment also induces the maturation of MDSCs into anti-tumor M1 macrophages.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3975103&req=5

Figure 1: Crosstalk between IL-1β and VEGF in the tumor microenvironment. (A) In the tumor microenvironment, IL-1β can be expressed initially by the malignant cells. In turn, IL-1β can recruit myeloid cells from the BM and further activate them to secrete pro-inflammatory and pro-angiogenic molecules, such as VEGF and IL-1β. Furthermore, IL-1β keeps myeloid cells in their immature stage, where they are pro-invasive and immunosuppressive. IL-1β can also activate tissue-resident ECs to produce VEGF and other pro-angiogenic factors. The malignant cells can also be activated by IL-1β for increased invasiveness. VEGF in the tumor microenvironment activates ECs and myeloid cells and also has homeostatic effects on these cells. (B) In the absence of IL-1β, inflammation, as well as VEGF production is diminished, which results in reduced invasiveness. Lack of IL-1β in the tumor microenvironment also induces the maturation of MDSCs into anti-tumor M1 macrophages.
Mentions: Finally, this review demonstrated the important role of the IL-1 family molecules, especially IL-1β, in the tumor microenvironment. IL-1β represents a major upstream cytokine that controls the local pro-inflammatory cascade and thereby affects the balance between protective immunity and destructive inflammation. IL-1 modulates diverse cells in the tumor microenvironment and acts together with VEGF in mounting and maintaining tumor-mediated angiogenesis (Figure 1). Thus, its neutralization should reduce tumor progression and invasiveness via its affect on pro-tumorigenic cells, and on the tumor-induced angiogenic switch. Further characterization of the optimal conditions for IL-1 neutralization could lead to the application of anti-IL-1 approaches in cancer therapy.

Bottom Line: IL-1 initiates and propagates inflammation, mainly by inducing a local cytokine network and enhancing inflammatory cell infiltration to affected sites and by augmenting adhesion molecule expression on ECs and leukocytes.In this review, we summarize the interactions between IL-1 and other pro-angiogenic factors during normal and pathological conditions.In addition, the feasibility of IL-1 neutralization approaches for anti-cancer therapy is discussed.

View Article: PubMed Central - PubMed

Affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev Beer-Sheva, Israel.

ABSTRACT
Tumor angiogenesis is one of the hallmarks of tumor progression and is essential for invasiveness and metastasis. Myeloid inflammatory cells, such as immature myeloid precursor cells, also termed myeloid-derived suppressor cells (MDSCs), neutrophils, and monocytes/macrophages, are recruited to the tumor microenvironment by factors released by the malignant cells that are subsequently "educated" in situ to acquire a pro-invasive, pro-angiogenic, and immunosuppressive phenotype. The proximity of myeloid cells to endothelial cells (ECs) lining blood vessels suggests that they play an important role in the angiogenic response, possibly by secreting a network of cytokines/chemokines and inflammatory mediators, as well as via activation of ECs for proliferation and secretion of pro-angiogenic factors. Interleukin-1 (IL-1) is an "alarm," upstream, pro-inflammatory cytokine that is generated primarily by myeloid cells. IL-1 initiates and propagates inflammation, mainly by inducing a local cytokine network and enhancing inflammatory cell infiltration to affected sites and by augmenting adhesion molecule expression on ECs and leukocytes. Pro-inflammatory mediators were recently shown to play an important role in tumor-mediated angiogenesis and blocking their function may suppress tumor progression. In this review, we summarize the interactions between IL-1 and other pro-angiogenic factors during normal and pathological conditions. In addition, the feasibility of IL-1 neutralization approaches for anti-cancer therapy is discussed.

No MeSH data available.


Related in: MedlinePlus