Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling

Boeck, Astrid De; Pauwels, Patrick; Hensen, Karen; Rummens, Jean-Luc; Westbroek, Wendy; Hendrix, An; Maynard, Dawn; Denys, Hannelore; Lambein, Kathleen; Braems, Geert; Gespach, Christian; Bracke, Marc; Wever, Olivier De

doi:10.1136/gutjnl-2011-301393

Cited by 143 publications

(129 citation statements)

References 53 publications

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“…Several studies demonstrated anti-tumor effects [8][9][10] whereas others showed tumor promoting effects [11][12][13] of MSCs in different tumor models. Regarding the effects on CRC, most of the studies have shown a pro-cancer effect of MSCs [29][30][31]. Consistently, we observed that trophic factors secreted by MSCs can promote colony formation and growth of a metastasis CRC cell line.…”

Section: Discussionsupporting

confidence: 71%

Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver

Hernanda¹,

Gonzalez²

2016

J Liver

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Colorectal Cancer (CRC) is the third most common cancer in the world. CRC tends to metastasize to the liver, which may occur in 20% to 70% of patients and represents the major cause of death. Mesenchymal Stem/stromal cells (MSCs) have shown to be able to migrate to CRC site and play an important role in tumor progression. We have previously identified a resident MSC population in the liver. Therefore, this study aims to investigate whether there is infiltration of MSCs into patient CRC Liver Metastasis (CRC-LM) and their potential effects on tumor cell growth. By culturing resected patient CRC-LM tissue, we observed the emerging of fibroblast-like cells. Further phenotype and functional characterization confirmed their bonafide MSCs features. In situ staining with a well-established MSCs marker showed a significant enrichment of candidate MSCs in patient CRC-LM, particularly the tumor-stromal area. Moreover, MSCs secreted trophic factors significantly increased colony formation and growth of a metastatic CRC cell line. In summary, we found infiltration and enrichment of MSCs in CRC-LM patient, which could in turn nourish tumor cells.

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Section: Discussionsupporting

confidence: 71%

Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver

Hernanda¹,

Gonzalez²

2016

J Liver

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“…DeBoeck et al [8] investigated the role of neuregulin-1 (tNRG1) and human epithelial growth factor regulator (HER), and reported that paracrine NRG1/HER3 signals initiated by MSCs promote CRC progression. In the present study, in vitro interactions between MSCs and CCC and potential mediators were further explored.…”

Section: Discussionmentioning

confidence: 99%

“…Despite this, our knowledge of colon cancer cell-MSC interactions remains limited, and the role of MSCs within colon tumours has yet to be elucidated. Only one recently published study exists in the literature regarding factors mediating CRC/MSC interactions which revealed that paracrine neuregulin-1/HER3 signals initiated by MSCs promote CRC tumour progression [8]. MSCs are known to secrete a wide range of pro-inflammatory chemokines [9] and are therefore likely to exert a significant effect on surrounding cells.…”

Section: Introductionmentioning

confidence: 99%

Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation

Hogan

Joyce

Murphy

et al. 2013

Biochemical and Biophysical Research Communications

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“…About 0.25 g of clean fresh tissue was cut into small pieces (1-2 mm 3 ), washed carefully with PBS, and incubated in 1 ml PBS for 1 hour at 37°C in a humidified CO 2 incubator. The samples were centrifuged 26 at 500 g for 10 minutes and 1500 g for 20 minutes. Without any further purification, 4 µl of the final supernatant (i.e.…”

Section: Fluorescent Labelling Of Mvs In Tumour Interstitial Fluidmentioning

confidence: 99%

“…To demonstrate the potential of the microfluidic chip with integrated planar waveguide as a diagnostic tool, fSPT measurements were performed on cell-derived MVs secreted in the interstitial fluid harvested from fresh human breast cancer specimens 26 . To ensure optimal fluorescent labelling of PS-exposing MVs present in the interstitial fluid, again an excess of dye-conjugated Annexin V was added.…”

Section: Size and Concentration Measurements Of Cell-derived Mvsmentioning

confidence: 99%

On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids

et al. 2014

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Cell-derived membrane vesicles that are released in biofluids, like blood or saliva, are emerging as potential non-invasive biomarkers for diseases, such as cancer. Techniques capable of measuring the size and concentration of membrane vesicles directly in biofluids are urgently needed. Fluorescence Single Particle Tracking microscopy has the potential of doing exactly that, by labelling the membrane vesicles with a fluorescent label and analysing their Brownian motion in the biofluid. However, unbound dye in the biofluid can cause high background intensity that strongly biases the fluorescence Single Particle Tracking size and concentration measurements. While such background can be avoided with light sheet illumination, current set-ups require specialty sample holders that are not compatible with high-throughput diagnostics. Here, a microfluidic chip with integrated light sheet illumination is reported, and accurate fluorescence Single Particle Tracking size and concentration measurements of membrane vesicles in cell culture medium and in interstitial fluid collected from primary human breast tumours are demonstrated.3

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Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling

Abstract: Paracrine NRG1/HER3 signals initiated by BM-MSC and T-MC promote CRC cell progression, and high tNRG1 expression is associated with poor prognosis in CRC.

Cited by 143 publications

References 53 publications

Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver

Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver

Impact of Mesenchymal Stem Cell secreted PAI-1 on colon cancer cell migration and proliferation

On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids

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