Culture supernatants of different colon cancer cell lines induce specific phenotype switching and functional alteration of THP-1 cells

Wu, Tsung‐Han; Li, Yingying; Wu, Tsung‐Chin; Chang, Jeng-Shou; Chou, Wen‐Chi; Hsieh, Ling–Ling; Chen, Jim-Ray; Yeh, Kun‐Yun

doi:10.1016/j.cellimm.2014.05.015

Cited by 33 publications

(37 citation statements)

References 22 publications

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“…In the past few years a revision of the strict M1/M2 model was suggested and a continuum of macrophage phenotypes ranging between the two extremes of pro- (M1) and anti-inflammatory (M2) types was proposed [ 12 ]. Our results are comparable to other studies on macrophage polarization using cytokines, tumour cells or tumour cell supernatants [ 11 ]. CD40 and IL-6, markers characteristic for M1 macrophages, were significantly elevated in IFN-γ/LPS polarized macrophages and the scavenger receptors CD36 and CD206, referred to M2, were significantly higher expressed in IL-4/IL-13 treated macrophages.…”

Section: Discussionsupporting

confidence: 91%

Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro

Estko

Baumgartner

Urech

et al. 2015

BMC Complement Altern Med

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BackgroundMacrophages are highly versatile cells that play an important role in tumour microenvironment. Tumour associated macrophages (TAMs) have been linked to both, good or bad prognosis of several cancer types depending on their number, composition and polarization. Viscum album lipophilic extract (VALE) contains several pentacyclic triterpenes known to modulate the activity of monocytes and other immune cells and to exhibit anticancer properties. In our in vitro study, we investigated the effect of tumour cell lines on macrophage polarization and monocyte chemotactic transmigration and examined the modulatory potential of VALE and its predominant triterpene oleanolic acid (OA).MethodsHuman peripheral blood monocytes were differentiated into monocyte derived macrophages (MDM) using M-CSF and polarized into M1 by IFN-γ and LPS and into M2 macrophages by IL-4 and IL-13 or by co-culture with two different tumour cell lines. Polarized macrophages were subsequently treated with VALE or OA. Phenotypic markers and cytokines were assessed by flow cytometry and immunoanalysis. Migration of human peripheral blood monocytes induced by monocyte chemotactic protein-1 (MCP-1) or supernatants of different tumour cell lines under the influence of VALE or OA was measured in a chemotaxis transmigration assay.ResultsIn vitro polarized M1 and M2 type macrophages revealed specific phenotypic patterns and tumour cell co-cultured MDM displayed ambiguous phenotypes with M1 as well as M2 associated markers. VALE and OA showed modest influence on cell surface marker profile and cytokine expression of tumour cell co-cultured macrophages. All tumour cell supernatants markedly enhanced the migratory activity of monocytes. VALE and OA significantly inhibited MCP-1 induced monocyte transmigration, whereas monocyte migration initiated by tumour cell derived supernatants was not affected.ConclusionsIn our study we reconfirmed that co-culture with different tumour cell lines can result in a mixed macrophage phenotype with M1 as well as M2 patterns, a finding that is important for a better understanding of tumour microenvironment functions. Moreover, we demonstrated that VALE shows slight immunomodulatory effects on tumour cell co-cultured macrophages and modulates monocyte chemotactic transmigration in vitro, indicating promising possibilities of triterpenes from Viscum album L. to contribute in a multimodal concept of anti-cancer therapy in future. Our data contribute to an understanding of monocyte function and macrophage polarization in vitro and of the possibility to influence their behaviour by triterpene containing mistletoe extracts.

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Section: Discussionsupporting

confidence: 91%

Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro

Estko

Baumgartner

Urech

et al. 2015

BMC Complement Altern Med

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“…M2 (tumor-associated) macrophages, when present in TME, correspond with a poor prognosis in several cancers, including tongue cancer [ 4 , 26 , 27 ]. Cancer cells through the conditioned media can polarize primary macrophages and the human monocytic cell line (THP-1) towards M2 [ 28 , 29 ]. We investigated whether this polarization effect could also be achieved using cancer cell EVs.…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between tongue carcinoma cells, extracellular vesicles, and immune cells in in vitro and in vivo models

et al. 2017

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The crosstalk between immune cells, cancer cells, and extracellular vesicles (EVs) secreted by cancer cells remains poorly understood. We created three-dimensional (3D) cell culture models using human leiomyoma discs and Myogel to study the effects of immune cells on highly (HSC-3) and less (SCC-25) invasive oral tongue squamous cell carcinoma (OTSCC) cell lines. Additionally, we studied the effects of EVs isolated from these cell lines on the cytotoxicity of CD8+ T and NK cells isolated from three healthy donors. Our analysis included the effects of these EVs on innate immunity in zebrafish larvae. Activated immune cells significantly decreased the proliferation of both OTSCC cell lines and associated with a diminished invasion area of HSC-3 cells. In general, EVs from SCC-25 increased the cytotoxic activity of CD8+ T and NK cells more than those from HSC-3 cells. However, this effect varied depending on the source and the immune and cancer cell subgroups. In zebrafish, the amount of IL-13 mRNA was decreased by SCC-25 EVs. This study describes promising in vitro and in vivo models to investigate interactions between immune cells, cancer cells, and EVs.

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“…The communication of macrophages with cancer cells, and how both populations influence each other, has been explored by several studies, at both cellular and molecular levels. Most of those in vitro studies rely on two main strategies, direct [ 31 , 32 ] or indirect [ 33 – 35 ] macrophage-cancer cell co-cultures or, alternatively, stimulation of one population with the supernatant of the other [ 36 , 32 , 37 ]. The preferential methodological approach seems to be indirect macrophage-cancer cell co-cultures, as this constitutes a simple and practical in vitro model.…”

Section: Discussionmentioning

confidence: 99%

“…The preferential methodological approach seems to be indirect macrophage-cancer cell co-cultures, as this constitutes a simple and practical in vitro model. These studies also frequently use macrophage-like cells differentiated from THP-1 human monocytes [ 33 , 35 , 36 ], upon stimulation with phorbol myristate acetate (PMA), although these are not completely representative of primary human macrophages [ 38 ]. Although the knowledge about macrophage-cancer cell communication has improved in the last years, there is scarce information on how ionizing radiation may modulate macrophage inflammatory profile and how the molecular crosstalk established between macrophages and cancer cells affects the radiation response of both populations.…”

Section: Discussionmentioning

confidence: 99%

Intricate Macrophage-Colorectal Cancer Cell Communication in Response to Radiation

Pinto

Velho

et al. 2016

PLoS ONE

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Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively. Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar fractionated scheme to that used during cancer patients’ treatment (2 Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co-culture with macrophages increased the mRNA expression of metabolism- and survival-related genes more in SW1463 than in RKO. The presence of macrophages also upregulated glucose transporter 1 expression in irradiated SW1463, but not in RKO cells. In addition, the influence of cancer cells on the expression of pro- and anti-inflammatory macrophage markers, upon radiation exposure, was also evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti-inflammatory CCL18. However, RKO cells induce an increase of macrophage pro-inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data demonstrated that macrophages and cancer cells mutually influence their response to radiation. Notably, conditioned medium from irradiated co-cultures increased non-irradiated RKO cell migration and invasion and did not impact on angiogenesis in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of primary human macrophage-cancer cell co-cultures revealed an intricate cell communication in response to ionizing radiation, which should be considered when developing therapies adjuvant to radiotherapy.

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Culture supernatants of different colon cancer cell lines induce specific phenotype switching and functional alteration of THP-1 cells

Cited by 33 publications

References 22 publications

Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro

Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro

Crosstalk between tongue carcinoma cells, extracellular vesicles, and immune cells in in vitro and in vivo models

Intricate Macrophage-Colorectal Cancer Cell Communication in Response to Radiation

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