Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines

Cortes-Dericks, Lourdes; Froment, Laurène; Kocher, Gregor J.; Schmid, Ralph A.

doi:10.1186/s13287-016-0282-7

Cited by 27 publications

(17 citation statements)

References 33 publications

(32 reference statements)

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“…It is postulated that the secretome may be responsible for bringing about cell death through necrosis or may be responsible in inducing the differentiation of cancer cells (Lee, Lee, & Kim, ). Human lung‐derived MSC‐CM has shown to inhibit the proliferation and reduce the viability of three malignant pleural mesothelioma cells that is a chemoresistant lung cancer, which is highly aggressive (Cortes‐Dericks, Froment, Kocher, & Schmid, ). Decreased tumour cell viability has also been reported using heat shock adipose stem cell‐derived conditioned media (ADSC‐CM) and amniotic‐derived stem cells via the induction of high nuclear condensation and growth cycle arrest (Cho et al, ).…”

Section: Paracrine Action Of Conditioned Media In Diseased Modelsmentioning

confidence: 99%

Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine

Gunawardena

Rahman

Abdullah

et al. 2019

J Tissue Eng Regen Med

100

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Recent studies suggest that the main driving force behind the therapeutic activity observed in mesenchymal stem cells (MSCs) are the paracrine factors secreted by these cells. These biomolecules also trigger antiapoptotic events to prevent further degeneration of the diseased organ through paracrine signalling mechanisms. In comparison with the normal physiological conditions, an increased paracrine gradient is observed within the peripheral system of diseased organs that enhances the migration of tissue-specific MSCs towards the site of infection or injury to promote healing.Thus, upon administration of conditioned media derived from mesenchymal stem cell cultures (MSC-CM) could contribute in maintaining the increased paracrine factor gradient between the diseased organ and the stem cell niche in order to speed up the process of recovery. Based on the principle of the paracrine signalling mechanism, MSC-CM, also referred as the secretome of the MSCs, is a rich source of the paracrine factors and are being studied extensively for a wide range of regenerative therapies such as myocardial infarction, stroke, bone regeneration, hair growth, and wound healing. This article highlights the current technological applications and advances of MSC-CM with the aim to appraise its future potential as a regenerative therapeutic agent.

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Section: Paracrine Action Of Conditioned Media In Diseased Modelsmentioning

confidence: 99%

Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine

Gunawardena

Rahman

Abdullah

et al. 2019

J Tissue Eng Regen Med

100

View full text Add to dashboard Cite

show abstract

“…Therefore, the MSC-derived conditioned medium (CM) (MSC-CM) has opposing effects on tumor development owing to different sources of the MSCs, compositions of the secreted factors or the biological context. Emerging evidence have emerged to demonstrate the functions and regulatory mechanisms of MSC-CM in various cancer types [ 4 , 5 ]. However, it has not been fully understood how human bone marrow MSC (BMSC)-CM affects hepatocellular carcinoma (HCC) cell properties, e.g.…”

Section: Introductionmentioning

confidence: 99%

Secretion of interleukin-6 by bone marrow mesenchymal stem cells promotes metastasis in hepatocellular carcinoma

Gong

2017

Bioscience Reports

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Mesenchymal stem cells (MSCs) interact with tumor cells and regulate tumorigenesis and metastasis. As one of the important components of the tumor microenvironment, MSC-secreted cytokines play a critical role in cancer development. However, whether and how bone marrow MSCs (BMSCs) and their secreted cytokines participate in hepatocellular carcinoma (HCC) progression, still remains largely unknown. In the present study, we first measured the concentration of interleukin-6 (IL-6) in BMSC conditioned medium (BMSC-CM). Next, we assessed the changes of invasion ability in response to treatment of BMSC-CM or recombinant IL-6 in two human HCC cell lines Bel-7404 and HepG2. Then we analyzed the level of key components of the IL-6 signal pathway, including IL-6 receptor and signal transducer (i.e. IL-6R and gp130), a transcription factor STAT3 (signal transducer and activator of transcription 3), as well as its target genes BCL2, CCND1, MCL1 and MMP2, in BMSC-CM or recombinant IL-6 treated Bel-7404 and HepG2 cells. Results showed that a considerable amount of IL-6 was secreted by BMSCs, and BMSC-CM markedly elevated Bel-7404 cell invasion rate and stimulated the signal transduction of IL-6/STAT3 pathway. Neutralizing the secreted IL-6 bioactivity by the anti-IL-6 antibody diminished the invasion-promoting effect and down-regulated IL-6/STAT3 pathway of BMSC-CM treated Bel-7404 cells. In conclusion, we found that BMSCs may activate the IL-6/STAT3 signaling pathway and promote cell invasion in Bel-7404 cells, suggesting that this protumor effect should be seriously considered before clinical application of MSC-mediated cancer therapy.

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“…We observed that ADSC-CM retained its anti-tumour activity even in its low molecular weight fraction (<30kDa). A few reports suggest that low molecular weight biomolecules present within the CM derived from MSCs are responsible for their tumour inhibitory activity (Cortes-Dericks et al, 2016;Ryu et al, 2014). Further, we also performed the molecular fractionation of ADSC-CM using 3kDa MWCO filters and measured tumour cell viability in the presence of <3kDa and >3kDa ADSC-CM fractions.…”

Section: Discussionmentioning

confidence: 98%

“…The intrinsic inhibitory effect of mesenchymal stem cells (MSCs) on tumour growth has been demonstrated with respect to various tumour cell lines such as breast cancer (Clarke et al, 2015), glioblastoma (Dasari et al, 2010;Ho et al, 2013;Yang et al, 2014), liver cancer (Qiao, Xu, Zhao, Ye, & Zhang, 2008), pancreatic cancer (Kidd et al, 2010), prostate cancer, colon cancer (Ohlsson et al, 2003), myeloma (Ciavarella et al, 2012), sarcoma (Khakoo et al, 2006), and lymphoma (Secchiero et al, 2010). Some of the anti-tumour effects contributed by MSCs have been attributed to the secreted factors released by them (Madrigal, demonstrated anti-tumour activity against various solid tumour types (Ahn et al, 2015;Cho et al, 2009;Cortes-Dericks et al, 2016;Ryu et al, 2014;Widowati et al, 2015). We examined the effect of secreted components present in the ADSC-conditioned medium (ADSC-CM) and their effect in combination with the Wnt antagonist secreted frizzled-related protein-4 (sFRP4) may generate enhanced anti-tumour activity in breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines

Visweswaran

Arfuso

Dilley

et al. 2018

The International Journal of Biochemistry & Cell Biology

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Tumours exhibit a heterogeneous mix of cell types that reciprocally regulate their growth in the tumour stroma, considerably affecting the progression of the disease. Both adipose-derived mesenchymal stem cells and Wnt signalling pathway are vital in driving breast tumour growth. Hence, we examined the effect of secreted factors released by adipose-derived mesenchymal stem cells, and further explored the anti-tumour property of the Wnt antagonist secreted frizzled-related protein 4 (sFRP4) on MCF-7 and MDA-MB-231 breast tumour cells. We observed that conditioned medium and extracellular matrix derived from adipose-derived mesenchymal stem cells inhibited tumour viability. The inhibitory effect of the conditioned medium was retained within its low molecular weight and non-protein component. The conditioned medium also induced apoptosis accompanied by a decrease in the mitochondrial membrane potential in tumour cells, Furthermore, it downregulated the protein expression of active β-catenin and Cyclin D1, which are major target proteins of the Wnt signalling pathway, and reduced the expression of anti-apoptotic protein Bcl-xL. The combination of conditioned medium and sFRP4 further potentiated the effects, depending on the tumour cell line and experimental assay. We conclude that factors derived from conditioned medium of adipose-derived mesenchymal stem cells and sFRP4 significantly decreased the tumour cell viability and migration rates (MCF-7), accompanied with an enhanced apoptotic activity through inhibition of canonical Wnt signalling. Besides giving an insight to possible paracrine interactions and influence of signalling pathways, reflective of a breast tumour microenvironment, this study emphasises the utilization of cell free-secreted factors and Wnt antagonists to improve conventional anti-cancer strategies.

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Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines

Cited by 27 publications

References 33 publications

Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine

Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine

Secretion of interleukin-6 by bone marrow mesenchymal stem cells promotes metastasis in hepatocellular carcinoma

The inhibitory influence of adipose tissue-derived mesenchymal stem cell environment and Wnt antagonism on breast tumour cell lines

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