Upregulation of IL‐6, IL‐8 and CXCL‐1 production in dermal fibroblasts by normal/malignant epithelial cells <i>in vitro</i>: Immunohistochemical and transcriptomic analyses

Kolář, Michal; Szabó, Pavol; Dvořánková, Barbora; Lacina, Lukáš; Gabius, Hans‐Joachim; Strnad, Hynek; Šáchová, Jana; Vlček, Čestmı́r; Plzák, Jan; Chovanec, Martin; Čada, Zdeněk; Betka, Jan; Fík, Zdeněk; Pačes, Jan; Kovářová, Hana; Motlı́k, Jan; Jarkovská, Karla; Smetana, Karel

doi:10.1111/boc.201200018

Cited by 71 publications

(73 citation statements)

References 46 publications

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“…Epithelial-fibroblast crosstalk can lead to changes in secreted factor profiles which can alter growth rates/migration of epithelial cells [40]. We did not find a differential effect of conditioned medium from these co-cultures on A549 proliferation.…”

Section: Discussionmentioning

confidence: 60%

Deficient repair response of IPF fibroblasts in a co-culture model of epithelial injury and repair

Prasad

Hogaboam

Járai

2014

Fibrogenesis Tissue Repair

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive disorder marked by relentless fibrosis and damage of the lung architecture. A growing body of evidence now suggests that IPF progresses as a result of aberrant epithelial-fibroblast crosstalk. Injured epithelia are a major source of growth factors such as PDGF which guide resident fibroblasts to injury sites.ResultsIn this study, we utilized a novel co-culture system to investigate the effect of fibroblast phenotype on their response to epithelial injury. Fibroblasts from normal lungs (NHLF) responded to epithelial injury and populated the wound site forming a fibroblast plug/mechanical barrier which prevented epithelial wound closure. IPF fibroblasts were impaired in their response to epithelial injury. They also expressed reduced PDGFRα compared to NHLFs and were defective towards PDGF-AA mediated directional movement. Neutralization of PDGF-AA and pan-PDGF but not PDGF-BB reduced the injury response of NHLFs thereby preventing the formation of the mechanical barrier and promoting epithelial wound closure. Co-culture of epithelial cells with IPF fibroblasts led to marked increase in the levels of pro-fibrotic growth factors - bFGF and PDGF and significant depletion of anti-fibrotic HGF in the culture medium. Furthermore, IPF fibroblasts but not NHLFs induced a transient increase in mesenchymal marker expression in the wound lining epithelial cells. This was accompanied by increased migration and faster wound closure in co-cultures with IPF fibroblasts.ConclusionsOur data demonstrate that the IPF fibroblasts have an aberrant repair response to epithelial injury.

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Section: Discussionmentioning

confidence: 60%

Deficient repair response of IPF fibroblasts in a co-culture model of epithelial injury and repair

Prasad

Hogaboam

Járai

2014

Fibrogenesis Tissue Repair

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“…This is consistent with the hypothesis that MIF could modulate the tumor size by inhibiting recruitment of cancer-associated fibroblasts (CAFs)/myofibroblasts, eventually resulting in retardation of tumor growth (7). These CAFs are known to be the source for effectors shaping a pro-tumoral microenvironment such as the chemokine CXCL-1 and interleukins-6 and -8 and may be involved in tumorigenesis (31,32). …”

Section: Discussionmentioning

confidence: 99%

Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer

et al. 2014

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Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor.

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“…Both tissues are composed from activated fibroblasts (producing the extracellular matrix, growth factors and other cytokines and chemokines), inflammatory cells and immature capillaries (56)(57)(58). Interestingly, cancer-associated fibroblasts (CAFs) of tumor stroma produce pro-inflammatory cytokines/chemokines such as interleukin 6 (IL6), IL8 and chemokine (C-X-C motif) ligand 1 (CXCL1) (59). Similar products can also be released from specialized inflammatory cells.…”

Section: Stroma As a Link Between Wound Healing And Cancer: Controllimentioning

confidence: 99%

Ageing as an Important Risk Factor for Cancer

Smetana

Lacina

Szabó

et al. 2016

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106

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Upregulation of IL‐6, IL‐8 and CXCL‐1 production in dermal fibroblasts by normal/malignant epithelial cells in vitro: Immunohistochemical and transcriptomic analyses

Abstract: Our results indicate an analogy between wound healing and tumour growth, support the importance of epithelial-mesenchymal interaction in this model system and establish a potential bio-inspired anticancer therapy.

Cited by 71 publications

References 46 publications

Deficient repair response of IPF fibroblasts in a co-culture model of epithelial injury and repair

Deficient repair response of IPF fibroblasts in a co-culture model of epithelial injury and repair

Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer

Ageing as an Important Risk Factor for Cancer

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