Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: Possible involvement of TNFα and IL‐1α

Ono, M.; Kiryu, Hiromaro; Furue, Masutaka; Ohmoto, Yasukazu; Nakayama, Juichiro; Nishioka, Yasuhiko; Sone, Saburo; Kuwano, Michihiko

doi:10.1002/(sici)1097-0215(20000115)85:2<182::aid-ijc6>3.3.co;2-d

Cited by 79 publications

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“…(16,17) It has been demonstrated that the tumor-associated macrophages produce some angiogenic factors, including VEGF, bFGF, PDGF, TNF-a and IL-8. (18,19) It is possible that, apart from secreting angiogenic factors themselves, TAMs can induce the production of these factors in the cancer cells. Liss et al have proposed that tumor cells might be activated by the macrophages and secrete angiogenic factors in head-and-neck squamous cell carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Interaction of monocytes/macrophages with ovarian cancer cells promotes angiogenesis in vitro

et al. 2013

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It has been established that macrophages and endothelial cells infiltrate peritoneum in the vicinity of tumor implants of epithelial ovarian cancer (EOC). This study investigates whether the interaction of ovarian cancer cells and tumor-associated macrophages could promote the involvement of endothelial cells in angiogenesis. Macrophage phenotypes were detected by fluorescence-activated cell sorting, and cytokine/chemokine secretion was measured by enzyme linked immunosorbent assay. The effect of co-culture of ovarian cancer cells and tumor-associated macrophage (TAM) cells on endothelial cell migration and tube formation was investigated. Signaling pathway mediators were also evaluated for their potential roles in endothelial cell activation by ovarian cancer cells co-cultured with TAM cells. Our results showed that higher expression of interleukin-8 (IL-8) expression associated with 54.26 ± 34.46% of TAM infiltration of peritoneum was significantly higher than 16.58 ± 17.74% of CD3 + T-cell by immunofluorescence co-staining and confocal microscopy. THP-1 cells exhibited M2-polarized phenotype markers with high proportion of CD68 + , CD206+ and CD204 + markers after phorbol 12-myristate 13-acetate (PMA) treatment, After co-culturing with TAM cells in a transwell chamber system, EOC cells (SKOV3) increased their IL-8 expression at the level of mRNA and protein. After exposure to the conditioned medium obtained by co-culturing TAM and SKOV3 cells, the migration and tube formation of endothelial cells were enhanced significantly. Furthermore, the upregulation of IL-8 expression in ovarian cancer cells induced by macrophages could be inhibited by pyrollidine dithiocarbamate, an inhibitor of nuclear factor (NF)-jB signal pathway. We suggest that the interaction of ovarian cancer cells and tumor-associated macrophages enhances the ability of endothelial cells to promote the progression of ovarian cancer. (Cancer Sci 2013; 104: 516-523) E pithelial ovarian cancer (EOC) accounts for 90% of all ovarian cancers and has become the leading cause of death from gynecological cancers in North America and Europe.(1)A remarkable feature of advanced EOC is the presence of widespread peritoneal metastases at the time of the initial diagnosis. However, the mechanisms of peritoneal seeding, spreading and progression remain elusive.Tumor microenvironment consists of various stromal cells, including activated endothelial cells, tumor-associated macrophages (TAMs), fibroblasts, and bone marrow-derived cells.(2)Our previous study has confirmed that more than 75% of mononuclear immune cells in peritoneum close to a tumor implant were TAM, which mimic chronic inflammation. Most studies reported that infiltrating TAMs were associated with cancer progression.(4-7) Tumor-associated macrophages might be recruited from peripheral blood by chemokines and then positioned in the tumor stroma. Those macrophages could be 'educated' and differentiated into M1 or M2 forms as a result of activation by some molecular factors. Interferon-c (IFN-c)

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Section: Discussionmentioning

confidence: 99%

Interaction of monocytes/macrophages with ovarian cancer cells promotes angiogenesis in vitro

et al. 2013

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“…Activation of the VEGF , IL‐8 , bFGF , and cyclooxygenase‐2 genes in both tumor cells and macrophages in the tumor stroma by inflammatory cytokines induces angiogenesis. ( 12,30 ) It has been reported that synergistic interaction between macrophages and tumor cells is required for tumor cell migration through a paracrine loop involving reciprocal signaling of EGF and colony‐stimulating factor‐1. ( 31 ) Inflammatory cytokines produced by macrophages affect tumor invasion and angiogenesis, suggesting that the recruitment of macrophages into the tumor stroma is prerequisite for the acquisition of malignant characteristics.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages

et al. 2008

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Attention has recently focused on the critical role of inflammatory responses in the tumor stroma that provide favorable conditions for cancer-cell growth and invasion/metastasis. In particular, macrophages recruited into the tumor stroma and activated, known as tumorassociated macrophages, are suggested to promote tumorigenesis. In this study, we examined the effect of a decrease in the number of monocytes/macrophages in peripheral blood and the tumor stroma on the development of bone and muscle metastases by lung cancer cells. M etastases of several malignant cancers including those of the breast, lung, prostate, and kidney have high affinity for bone. Bone metastasis is often accompanied by serious complications such as pathological fractures, bone pain, spinal cord compression, and hypercalcemia. Organ metastasis, including that affecting bone, is a multistep process mediated through mutual interaction between cancer cells and the host microenvironment. In bone metastasis, cancer cells reach the bone via hematogenous spread, followed by osteoclastic bone resorption, and finally proliferate in the bone matrix.(1,2)Moreover, osteoclast-stimulating cytokines such as PTHrP have been shown to promote bone metastasis. Inflammatory responses in the tumor stroma play an important role by providing favorable conditions for cancer cell growth, invasion/metastasis, and angiogenesis as well as malignant progression.(4-6) In particular, monocytes/macrophages are recruited into the tumor stroma, and activated macrophages known as TAMs produce potent angiogenic factors, as well as inflammatory cytokines, growth factors, and proteases, resulting in a promotion of angiogenesis and invasion/metastasis.(7-9) Infiltrating TAMs are often closely associated with poor prognosis and tumor angiogenesis in patients with various tumor types.(9-11) A preparation of Cl 2 MDP-LIP has been reported to markedly inhibit angiogenesis in corneas in response to inflammatory cytokines through depletion of macrophages.(12) A recent study has demonstrated that administration of clodronate-liposomes depleted TAMs in mouse models resulting in significant inhibition of tumor growth and tumor angiogenesis, whereas free clodronate alone did not.(13) Clodronate-liposomes were also found to inhibit both tumor growth and tumor angiogenesis by lung cancer cells in a xenograft model when stimulated by inflammatory stimuli. (14) Angiogenesis in a tumor microenvironment in bone marrow also played a critical role in the induction of an angiogenic response and invasion/metastasis by cancer cells.(15) Furthermore, monocyte/macrophage precursor cells entered the osteoclastic lineage and expressed the osteoclastic marker TRAP under the influence of the RANK/RNAKL signaling pathway.(16) Tumor burden at bone metastatic sites was markedly decreased in preclinical models on treatment with inhibitors of the RANK/RANKL pathway and neutralizing antibodies against PTHrP as well as bisphosphonate, suggesting a central role for osteoclasts in bone metastasis. (17)(18)(19) ...

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“…We found a significant correlation between the number of infiltrating macrophages and the microvascular density or tumor progression levels in glioblastomas and melanoma. ( 16,17 ) Taken together, increased numbers of TAM are significantly associated with poor prognosis, suggesting their role in the malignant progression of most solid tumors.…”

Section: Macrophages Are Educated To Promote Tumor Growth Angiogenesmentioning

confidence: 98%

Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy

Ono¹

2008

Cancer Science

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Macrophage infiltration correlates with tumor stage and angiogenesis in human malignant melanoma: Possible involvement of TNFα and IL‐1α

Cited by 79 publications

References 0 publications

Interaction of monocytes/macrophages with ovarian cancer cells promotes angiogenesis in vitro

Interaction of monocytes/macrophages with ovarian cancer cells promotes angiogenesis in vitro

Inhibition of bone and muscle metastases of lung cancer cells by a decrease in the number of monocytes/macrophages

Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy

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