Stromal Fibroblasts in Colorectal Liver Metastases Originate From Resident Fibroblasts and Generate an Inflammatory Microenvironment

Müeller, Lars; Goumas, Freya A.; Affeldt, Marianne; Sandtner, Susanne; Gehling, Ursula M.; Brilloff, Silke; Walter, Jessica; Karnatz, Nadia; Lamszus, Katrin; Rogiers, Xavier; Bröering, Dieter C.

doi:10.2353/ajpath.2007.060661

Cited by 158 publications

(120 citation statements)

References 47 publications

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“…Therefore, the activation of an inflammatory tumor microenvironment may depend at least partly on fibroblasts. In agreement with this finding, Mueller et al 41 recently reported that stromal fibroblasts could generate an inflammatory microenvironment to promote colorectal liver metastases. In addition, recently Erez et al 42 demonstrated that cancerassociated fibroblasts mediate tumor-enhancing inflammation in a nuclear factor-B-dependent manner.…”

Section: Discussionsupporting

confidence: 68%

FSP1+ Fibroblasts Promote Skin Carcinogenesis by Maintaining MCP-1-Mediated Macrophage Infiltration and Chronic Inflammation

Zhang

Chen

Xiao

et al. 2011

The American Journal of Pathology

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Cancer development is often associated with increased fibroblast proliferation and extensive fibrosis; however, the role of fibroblasts during carcinogenesis remains largely unknown. Using the 7,12-dimethylbenz-(a)anthracene and 12-O-tetradecanoylphorbol-13-acetateinduced two-stage skin carcinogenesis model, we demonstrated here that there was a massive accumulation and proliferation of fibroblasts in the skin shortly after application of carcinogen. Selective abatement of these cells during the promotion stage drastically decreased incidence and progression of papillomas. This correlated well with reduced macrophage infiltration and impaired cytokine storm in the affected skin. 12-O-tetradecanoylphorbol-13-acetate stimulated skin fibroblasts, secreting high levels of monocyte chemotactic protein-1, and neutralization of this chemokine eliminated almost completely the fibroblast-induced chemotaxis of macrophages. These results strongly suggest that fibroblasts promote skin tumor development by producing monocyte chemotactic protein-1 and maintaining chronic inflammation.

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Section: Discussionsupporting

confidence: 68%

FSP1+ Fibroblasts Promote Skin Carcinogenesis by Maintaining MCP-1-Mediated Macrophage Infiltration and Chronic Inflammation

Zhang

Chen

Xiao

et al. 2011

The American Journal of Pathology

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“…Other studies also support a role for inflammatory mediators in activating fibroblasts derived from other tumour types including TNF-α-induced expression of the pro-angiogenic chemokine CXCL8/IL-8 in liver fibroblasts, also in an NF-κB-dependent manner [57]. Similarly, TNF-α induces IL-6 and the chemokine CCL2 in CAFs derived from colorectal liver metastases [58].…”

Section: Activation By Paracrine Signallingmentioning

confidence: 88%

From sentinel cells to inflammatory culprits: cancer‐associated fibroblasts in tumour‐related inflammation

Servais

Erez

2012

The Journal of Pathology

130

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“…30 We previously detected TNF-a expression in colon tissues in this model. 9 Indeed, TNF-a in vitro augmented cell proliferation and HB-EGF expression in colonic fibroblasts equally as well as CCL3.…”

Section: Discussionmentioning

confidence: 99%

Crucial involvement of the CCL3-CCR5 axis-mediated fibroblast accumulation in colitis-associated carcinogenesis in mice

et al. 2014

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Patients with inflammatory bowel diseases often develop colon carcinoma. Combined treatment of azoxymethane (AOM) and dextran sulfate sodium (DSS) recapitulates colitis‐associated cancer in mice. AOM/DSS‐induced tumor formation was reduced in CCL3‐ or its specific receptor, CCR5‐deficient mice despite the presence of a massive infiltration of inflammatory cells. However, AOM/DSS‐induced type I collagen‐positive fibroblast accumulation in the colon was reduced in CCL3‐ or CCR5‐deficient mice. This was associated with depressed expression of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF), which is expressed mainly by fibroblasts. Moreover in vitro, CCL3 induced fibroblasts to proliferate and to enhance HB‐EGF expression. Furthermore, CCR5 blockade reduced tumor formation together with reduced fibroblast accumulation and HB‐EGF expression, even when administered after the development of multiple colon tumors. Thus, CCL3‐CCR5‐mediated fibroblast accumulation may be required, in addition to leukocyte infiltration, to induce full‐blown colitis‐associated carcinogenesis. Our studies shed light on a therapeutic potential of CCR5 antagonist for patients with colitis‐associated cancer.

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Stromal Fibroblasts in Colorectal Liver Metastases Originate From Resident Fibroblasts and Generate an Inflammatory Microenvironment

Cited by 158 publications

References 47 publications

FSP1+ Fibroblasts Promote Skin Carcinogenesis by Maintaining MCP-1-Mediated Macrophage Infiltration and Chronic Inflammation

FSP1+ Fibroblasts Promote Skin Carcinogenesis by Maintaining MCP-1-Mediated Macrophage Infiltration and Chronic Inflammation

From sentinel cells to inflammatory culprits: cancer‐associated fibroblasts in tumour‐related inflammation

Crucial involvement of the CCL3-CCR5 axis-mediated fibroblast accumulation in colitis-associated carcinogenesis in mice

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