Tumor associated macrophages provide the survival resistance of tumor cells to hypoxic microenvironmental condition through IL-6 receptor-mediated signals

Jeong, Soo Kyung; Kim, Joong Sun; Lee, Chang Geun; Park, You-Soo; Kim, Sung Dae; Yoon, Sun Woo; Han, Dong Hoon; Lee, Kyu Yeol; Jeong, Min Ho; Jo, Wol Soon

doi:10.1016/j.imbio.2015.11.010

Cited by 47 publications

(39 citation statements)

References 45 publications

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“…These results are consistent with macrophage behavior in spheroids and in vivo in which IFNg+LPS stimulated macrophages infiltrate the hypoxic core of spheroids (Supplemental Fig. 12) and hypoxic regions of tumors 19 . Interestingly, the area of stable 4T1 disks decreased following the injection of unstimulated macrophages.…”

supporting

confidence: 86%

Anin vitrotumorigenesis model based on live cell-generated oxygen and nutrient gradients

Gilmore

Flaherty

Somasundaram

et al. 2020

Preprint

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The tumor microenvironment (TME) is multi-cellular, spatially heterogenous, and contains cell-generated gradients of soluble molecules. Current cell-based model systems lack this complexity or are difficult to interrogate microscopically. We present a 2D live-cell chamber that approximates the TME and demonstrate that breast cancer cells and macrophages generate hypoxic and nutrient gradients, self-organize, and have spatially varying phenotypes along the gradients, leading to new insights into tumorigenesis.

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supporting

confidence: 86%

Anin vitrotumorigenesis model based on live cell-generated oxygen and nutrient gradients

Gilmore

Flaherty

Somasundaram

et al. 2020

Preprint

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“…Based on our data, we suggest that the IL-6 secreted by THP-1 cells may be the one of the major cytokines that trigger the MEK/Erk activation in radioresistant lung cancer cells. Jeong et al (49) demonstrated the M2 TAM-activated MEK/Erk signaling pathway in breast cancer cells, and IL-6 triggered-MEK/ERK activation in other types of cancer cells has also previously been demonstrated (50,51). However, IL-6 may not be the only molecule contained in THP-1 CM and may trigger MEK/Erk activation.…”

Section: Discussionmentioning

confidence: 97%

Increased infiltration of macrophages to radioresistant lung cancer cells contributes to the development of the additional resistance of tumor cells to the cytotoxic effects of NK cells

Shen

Chen

et al. 2018

Int J Oncol

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In this study, in order to investigate the effects of increased macrophage infiltration to radioresistant lung tumors in regulating natural killer (NK) cell-mediated immunity, we examined whether the treatment of radioresistant cells with conditioned medium (CM) from phorbol myristate acetate (PMA)/interleukin (IL)-4 treated THP-1 cells (used as a tumor-associated macrophage source) leads to the development of the additional resistance of tumor cells to NK cell cytotoxicity. We found that the susceptibility of THP-1 CM-treated radioresistant cells to NK cell cytotoxicity was decreased compared to the non-treated cells. In addition, it was found that such a decreased susceptibility was associated with increased programmed death receptor ligand 1 (PD-L1) and decreased natural killer group 2D (NKG2D) ligand levels in tumor cells. We further discovered that the THP-1 cells secreted a high level of IL-6, and that blocking IL-6 action by the addition of a neutralizing antibody (Ab) for IL-6 into the THP-1 CM decreased the resistance of THP-1 CM-treated radioresistant cells to NK cell cytotoxicity. Moreover, we discovered that MEK/Erk was the most critical IL-6 downstream signaling pathway in triggering the THP-1 CM effect; thus, the addition of MEK/Erk inhibitor to THP-1 CM enhanced the susceptibility of the THP-1 CM-treated radioresistant cells to NK cell cytotoxicity. On the whole, the findings of this study suggest the existence of a malignant loop characterized by increased macrophage infiltration into radioresistant cells which, in turn, promotes the development of the additional resistance of these cells to NK cell cytotoxicity.

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“…TNF‐α is one of the key tumor‐associated cytokines driving TAMs toward a VEGF‐C‐expressing phenotype. In addition to pro‐lymphangiogenic factors, TAMs can produce and secrete extracellular matrix remodeling mediators (metalloproteinases) which further support tumor vascularisation, including lymphangiogenesis . Several studies have demonstrated that the secretion of factors such as matrix metalloproteinase‐9 or VEGF by multi‐nucleated giant macrophages is associated with vascular invasion of bone tumors during cancer metastasis .…”

Section: More Than a Passive Conduit: Lymphatic Tracks May Modulate Gmentioning

confidence: 99%

Granulomatous Inflammation in Tuberculosis and Sarcoidosis: Does the Lymphatic System Contribute to Disease?

2019

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A striking and unexplained feature of granulomatous inflammation is its anatomical association with the lymphatic system. Accumulating evidence suggests that lymphatic tracks and granulomas may alter the function of each other. The formation of new lymphatics, or lymphangiogenesis, is an adaptive response to tumor formation, infection, and wound healing. Granulomas also may induce lymphangiogenesis which, through a variety of mechanisms, could contribute to disease outcomes in tuberculosis and sarcoidosis. On the other hand, alterations in lymph node function and lymphatic draining may be primary events which attenuate the risk and severity of granulomatous inflammation. This review begins with an introduction of granulomatous inflammation and the lymphatic system. A role of the lymphatic system in tuberculosis and sarcoidosis is then hypothesized. With a focus on lymphangiogenesis in these diseases, and on the potential for this process to promote dissemination, parallels are established with the well-established role of lymphangiogenesis in tumor biology.

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Tumor associated macrophages provide the survival resistance of tumor cells to hypoxic microenvironmental condition through IL-6 receptor-mediated signals

Cited by 47 publications

References 45 publications

Anin vitrotumorigenesis model based on live cell-generated oxygen and nutrient gradients

Anin vitrotumorigenesis model based on live cell-generated oxygen and nutrient gradients

Increased infiltration of macrophages to radioresistant lung cancer cells contributes to the development of the additional resistance of tumor cells to the cytotoxic effects of NK cells

Granulomatous Inflammation in Tuberculosis and Sarcoidosis: Does the Lymphatic System Contribute to Disease?

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