Human mesenchymal stem cells enhance cancer cell proliferation via IL-6 secretion and activation of ERK1/2

Scherzad, Agmal; Steber, Magdalena; Gehrke, Thomas; Rak, Kristen; Froelich, Katrin; Schendzielorz, Philipp; Hagen, Rudolf; Kleinsasser, Norbert; Hackenberg, Stephan

doi:10.3892/ijo.2015.3009

Cited by 37 publications

(33 citation statements)

References 43 publications

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“…IL-6 and IL-8 are chemotactic cytokines and mediators of stem cell activation [54]. Furthermore, MSCs promote tumor cell progression via IL-6 secretion and proangiogenic factors [55]. In contrast to the present study, other metal oxide nanoparticles, such as silver oxide NPs [32] and zinc oxide NPs [56], lead to the increased secretion of those cytokines.…”

Section: Discussioncontrasting

confidence: 80%

Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

Radeloff

Tirado

et al. 2020

Nanomaterials

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Magnetic nanoparticles (NPs), such as very small iron oxide NPs (VSOPs) can be used for targeted drug delivery, cancer treatment or tissue engineering. Another important field of application is the labelling of mesenchymal stem cells to allow in vivo tracking and visualization of transplanted cells using magnetic resonance imaging (MRI). For these NPs, however, various toxic effects, as well as functional impairment of the exposed cells, are described. The present study evaluates the influence of VSOPs on the multilineage differentiation ability and cytokine secretion of human adipose tissue derived stromal cells (hASCs) after long-term exposure. Human ASCs were labelled with VSOPs, and the efficacy of the labelling was documented over 4 weeks in vitro cultivation of the labelled cells. Unlabelled hASCs served as negative controls. Four weeks after labelling, adipogenic and osteogenic differentiation was histologically evaluated and quantified by polymerase chain reaction (PCR). Changes in gene expression of IL-6, IL-8, VEGF and caspase 3 were determined over 4 weeks. Four weeks after the labelling procedure, labelled and unlabelled hASCs did not differ in the gene expression of IL-6, IL-8, VEGF and caspase 3. Furthermore, the labelling procedure had no influence on the multidifferentiation ability of hASC. The percentage of labelled cells decreased during in vitro expansion over 4 weeks. Labelling with VSOPs and long-term intracellular disposition probably have no influence on the physiological functions of hASCs. This could be important for the future in vivo use of iron oxide NPs.

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Section: Discussioncontrasting

confidence: 80%

Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

Radeloff

Tirado

et al. 2020

Nanomaterials

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“…Both TNF‐ and TNF/IL‐6–treated BMMs expressed markers of osteoclast differentiation (Figure C), but only the latter formed multinucleated osteoclasts (Figures A and B and Figures C and D). Removing IL‐6 on day 2 of culture reduced, but did not eliminate, RANKL‐independent osteoclastogenesis (Supplementary Figure 3A, available at http://onlinelibrary.wiley.com/doi/10.1002/art.39837/abstract), suggesting that IL‐6 may have pro‐proliferative effects on precursors . Indeed, RANKL and TNF inhibited proliferation compared to M‐CSF alone, while IL‐6 promoted proliferation in the presence of TNF to levels similar to those of M‐CSF alone (Supplementary Figure 3B).…”

Section: Resultsmentioning

confidence: 97%

RANK‐Independent Osteoclast Formation and Bone Erosion in Inflammatory Arthritis

O’Brien

Fissel

Maeda

et al. 2016

Arthritis & Rheumatology

119

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Objective Pro-inflammatory molecules promote osteoclast-mediated bone erosion by upregulating local RANKL production. However, recent evidence suggests that combinations of cytokines, such as TNFα plus IL-6, induce RANKL-independent osteoclastogenesis. This study sought to better understand TNFα/IL-6 induced osteoclast formation, and to determine whether RANK is absolutely required for osteoclastogenesis and bone erosion in murine inflammatory arthritis. Methods Myeloid precursors from wild-type (WT) mice, or mice with either germline or conditional deletion of Rank, Nfatc1, Dap12 or Fcrg, were treated with either RANKL, or TNFα plus IL-6. Osteoprotegerin, anti-IL-6 receptor (IL6R) and hydroxyurea were used to block RANKL, the IL6R and cell proliferation, respectively. Clinical scoring, histology, micro-computed tomography and qPCR were employed to evaluate K/BxN serum transfer arthritis in WT and RANK-deleted mice. Loss of Rank was verified by qPCR and by performing osteoclast cultures. Results TNFα/IL-6 generated osteoclasts in vitro that resorbed mineralized tissue through a pathway dependent on IL6R, NFATc1, DAP12 and cell proliferation, but independent of RANKL or RANK. Bone erosion and osteoclast formation were reduced, but not absent, in arthritic mice with inducible deficiency of RANK. TNFα/IL-6, but not RANKL, induced osteoclast formation in bone marrow and synovial cultures from RANK-deficient animals. Multiple IL-6 family members (IL-6, LIF, OSM) were upregulated in the synovium of arthritic mice. Conclusion The persistence of bone erosion and synovial osteoclasts in RANK-deficient mice, and the ability of TNFα/IL-6 to induce osteoclastogenesis, suggest more than one cytokine pathway exists to generate these bone resorbing cells in inflamed joints.

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“…Activation of ERK1/2 by MSC-CM was also reported by Scherzad et al . They showed that proliferation of head and neck squamous cell lines cultured in MSC-CM was induced by soluble mediators secreted by MSCs, mainly IL-6 56 .…”

Section: Discussionmentioning

confidence: 99%

The interplay between adipose-derived stem cells and bladder cancer cells

Maj

Kokocha

Bajek

et al. 2018

Sci Rep

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Tissue engineering approaches offer alternative strategies for urinary diversion after radical cystectomy. Possible triggering of cancer recurrence remains, however, a significant concern in the application of stem-cell based therapies for oncological patients. Soluble mediators secreted by stem cells induce tissue remodelling effects, but may also promote cancer cells growth and metastasis. We observed a substantial increase in the concentration of IL-6 and IL-8 in the secretome of adipose-derived stem cells (ASCs) co-cultured with bladder cancer cells. Concentrations of GM-CSF, MCP-1 and RANTES were also elevated. Bioactive molecules produced by ASCs increased the viability of 5637 and HT-1376 cells by respectively 15.4% and 10.4% (p < 0.0001). A trend in reduction of adhesion to ECM components was also noted, even though no differences in β-catenin expression were detected. When HT-1376 cells were co-cultured with ASCs their migration and invasion increased by 24.5% (p < 0.0002) and 18.2% (p < 0.002). Expression of p-ERK1/2 increased in 5637 cells (2.2-fold; p < 0.001) and p-AKT in HB-CLS-1 cells (2.0-fold; p < 0.001). Our results confirm that ASCs crosstalk with bladder cancer cells in vitro what influences their proliferation and invasive properties. Since ASCs tropism to tumour microenvironment is well documented their application towards post-oncologic reconstruction should be approached with caution.

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Human mesenchymal stem cells enhance cancer cell proliferation via IL-6 secretion and activation of ERK1/2

Cited by 37 publications

References 43 publications

Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

RANK‐Independent Osteoclast Formation and Bone Erosion in Inflammatory Arthritis

The interplay between adipose-derived stem cells and bladder cancer cells

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