Cancer-Associated Fibroblasts, a Parameter of the Tumor Microenvironment, Are Associated With Poor Prognosis in Esophageal Squamous Cell Cancer After Surgery

Cheng, Yufeng; Wang, K.; Ma, Wen‐Jie; Song, Yawei; Wang, J.; Wang, N.; Jia, Yibin; Bai, Bing

doi:10.1016/j.ijrobp.2013.06.762

Cited by 21 publications

(31 citation statements)

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“…Using a step-by-step selecting approach, we identified a total of 17 publications with 18 cohorts of patients for this study [ 11 , 16 – 22 , 26 – 34 ] ( Fig 1 ). The characteristics of the included studies are shown in Tables 1 and 2 , Tables A, B and C in S1 File .…”

Section: Resultsmentioning

confidence: 99%

“…From the published studies [ 24 , 25 ], survival data were extracted from tables or using Kaplan-Meier curves using a digitizing software tool (Engauge Digitizer version 4.1), which converted graphs into data for both groups. One study reported the hazard ratio and its 95% confidence interval for 3-year overall survival and disease-fres survival, and we used these data directly in the subsequent combined analysis [ 26 ]. Disagreements regarding extracted data were resolved by consensus.…”

Section: Methodsmentioning

confidence: 99%

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Stromal Myofibroblasts Are Associated with Poor Prognosis in Solid Cancers: A Meta-Analysis of Published Studies

Liu¹,

Liu²,

Yao³

et al. 2016

PLoS ONE

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ObjectivePublished studies have evaluated the impact of stromal myofibroblasts on prognosis in solid cancers. However, the results of these studies remain controversial. We therefore performed a meta-analysis to address this issue.MethodsThe PubMed, ISI Web of Science and Embase databases were searched through November 30th, 2015 by two investigators, and a total of 17 studies that contained 2606 patients were included. Stromal myofibroblasts were quantified in solid cancers using α-smooth muscle actin staining. Pooled Odds Ratio with 95% Confidence Intervals were calculated, and publication bias was analyzed.ResultsThe results of this study suggest that in solid cancers, a high density of stromal myofibroblasts is significantly associated with poor 3- and 5-year overall survival (pooled odds ratio (95% confidence interval): 1.33 (1.10–1.60) for 3-year overall survival and 1.68 (1.22–2.32) for 5-year overall survival). In addition, a high density of stromal myofibroblasts also predicted poor 3- and 5-year disease-free survival (1.30 (1.05–1.60) for 3-year disease-free survival and 1.36 (1.01–1.83) for 5-year disease-free survival). However, stromal myofibroblasts were not associated with 3- and 5-year cancer-specific survival. No publication bias was found for all analyses.ConclusionsThe results of this study suggest that a high density of stromal myofibroblasts is associated with poor survival in solid cancers. More studies were required to investigate the prognostic value of stromal myofibroblasts in different types of solid cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Stromal Myofibroblasts Are Associated with Poor Prognosis in Solid Cancers: A Meta-Analysis of Published Studies

Liu¹,

Liu²,

Yao³

et al. 2016

PLoS ONE

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“…They create a microenvironment that promotes cancer growth, invasiveness, vascularization, establishment of the premetastatic niche, metastasis, and therapy resistance (7)(8)(9)(10). Moreover, the presence of CAFs in vivo correlates with poor prognosis of several cancer types (11)(12)(13)(14). Therapeutics targeting CAF activation may therefore be attractive, but the mechanisms responsible for the transformation of HFs into CAFs are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Exosomes Induce Fibroblast Differentiation into Cancer-Associated Fibroblasts through TGFβ Signaling

Goulet

Bernard

Tremblay³

et al. 2018

Molecular Cancer Research

222

145

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A particularly important tumor microenvironment relationship exists between cancer cells and surrounding stromal cells. Fibroblasts, in response to cancer cells, become activated and exhibit myofibroblastic characteristics that favor invasive growth and metastasis. However, the mechanism by which cancer cells promote activation of healthy fibroblasts into cancer-associated fibroblasts (CAF) is still not well understood. Exosomes are nanometer-sized vesicles that shuttle proteins and nucleic acids between cells to establish intercellular communication. Here, bladder cancer-derived exosomes were investigated to determine their role in the activation of healthy primary vesical fibroblasts. Exosomes released by bladder cancer cells are internalized by fibroblasts and promoted the proliferation and expression of CAF markers. In addition, cancer cell-derived exosomes contain TGFβ and in exosome-induced CAFs SMAD-dependent signaling is activated. Furthermore, TGFβ inhibitors attenuated CAF marker expression in healthy fibroblasts. Therefore, these data demonstrate that bladder cancer cells trigger the differentiation of fibroblasts to CAFs by exosomes-mediated TGFβ transfer and SMAD pathway activation. Finally, exosomal TGFβ localized inside the vesicle and contributes 53.4% to 86.3% of the total TGFβ present in the cancer cell supernatant. This study highlights a new function for bladder cancer exosomes as novel modulators of stromal cell differentiation. This study identifies exosomal TGFβ as new molecular mechanism involved in cancer-associated fibroblast activation. .

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“…Nevertheless, podoplanin is not restricted to the endothelial level, its expression also being evidenced in basal cells of the stratified epithelium that lines the oral cavity (4) and basal epithelial cells of the uterine cervix (5,6). At the level of the stromal compartment, podoplanin expression is not only increased in myofibroblast-like cells type, its weak expression in normal connective tissue being well known, but also in pathological situations such as Dupuytren disease or in tumor-associated stroma (7). In the normal ovary, podoplanin expression has been less characterized, not only concerning its endothelial expression, but also its expression in the ovarian stroma.…”

mentioning

confidence: 99%

Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer

Cobec

Sas

Pirtea

et al. 2016

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LMVDT correlated with proliferating tumor vessels located in the peritumoral area (p=0.024) and with the number of mature vessels located in the intratumoral area (p<0.0001), while LMVDP correlated with peritumoral mature vessels (p<0.000l). Proliferating tumor cells at the invasive front were highly positive for podoplanin. To the best of our knowledge, this study represents the first assessment of lymphatic endothelial cell proliferation correlated with podoplanin expression in tumor cells from ovarian cancer. Our data support podoplanin as a potential target that may help reduce ovarian cancer dissemination and lymphatic metastasis.

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Cancer-Associated Fibroblasts, a Parameter of the Tumor Microenvironment, Are Associated With Poor Prognosis in Esophageal Squamous Cell Cancer After Surgery

Cited by 21 publications

References 0 publications

Stromal Myofibroblasts Are Associated with Poor Prognosis in Solid Cancers: A Meta-Analysis of Published Studies

Stromal Myofibroblasts Are Associated with Poor Prognosis in Solid Cancers: A Meta-Analysis of Published Studies

Exosomes Induce Fibroblast Differentiation into Cancer-Associated Fibroblasts through TGFβ Signaling

Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer

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