TGFBI Expression in Cancer Stromal Cells is Associated with Poor Prognosis and Hematogenous Recurrence in Esophageal Squamous Cell Carcinoma

Ozawa, Daigo; Yokobori, Takehiko; Sohda, Makoto; Sakai, Makoto; Hara, Keigo; Honjo, Hiroaki; Kato, Hiroyuki; Miyazaki, Tatsuya; Kuwano, Hiroyuki

doi:10.1245/s10434-014-4259-4

Cited by 37 publications

(34 citation statements)

References 24 publications

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“…TGFβ1 was reported to attenuate cancer cell sensitivity to chemoradiotherapy via several mechanisms in human cancers . In ESCC, TGFβ1 was found to be mainly expressed in stromal fibroblasts . Our study aimed to investigate whether paracrine TGFβ1 signaling was involved in CAFs‐conferred chemoresistance of ESCC cells.…”

Section: Resultsmentioning

confidence: 97%

Cancer‐associated fibroblasts mediated chemoresistance by a FOXO1/TGFβ1 signaling loop in esophageal squamous cell carcinoma

Zhang

Xie

Yue

et al. 2016

Molecular Carcinogenesis

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Previous studies on the mechanisms underlying ESCC (esophageal squamous cell carcinoma) chemoresistance only focused on tumor cells while tumor microenvironment has been completely ignored. Our study aimed to clarify the effect of CAFs (cancer-associated fibroblasts), one major component of tumor microenvironment, on the chemoresistance of ESCC. By primary culture, two pairs of CAFs and matched NFs (normal fibroblasts) were isolated from tumor tissues of ESCC patients and matched normal esophageal epithelial tissues, respectively. The association of CAFs and chemoresistance was assessed in esophageal carcinoma cells, in xenograft tumor models and in clinical specimens of ESCC patients. We found CAFs conferred ESCC cells significant resistance to several common chemotherapeutic drugs including cisplatin, taxol, irinotecan (CPT-11), 5-fluorouracil (5-Fu), carboplatin, docetaxel, pharmorubicin, and vincristine. Mechanism studies revealed that blockage of CAFs-secreted TGFβ1 signaling by its receptor TGFβR1 inhibitor LY2157299 significantly reversed the chemoresistance in vitro and in vivo. Furthermore, the crosstalk of CAFs and ESCC cells enhanced the expression and activation of FOXO1, a member of the forkhead transcription factors in the O-box sub-family, inducing TGFβ1 expression in an autocrine/paracrine signaling loop. In 130 ESCC patients, the expression of TGFβ1 in CAFs was significantly associated with overall survival of patients treated with chemoradiotherapy. Together, our study highlighted TGFβ1 expressed in CAFs as an attractive target to reverse tumor chemoresistance, and can be used as an independent prognostic factor of ESCC patients treated with chemoradiotherapy. © 2016 Wiley Periodicals, Inc.

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Section: Resultsmentioning

confidence: 97%

Cancer‐associated fibroblasts mediated chemoresistance by a FOXO1/TGFβ1 signaling loop in esophageal squamous cell carcinoma

Zhang

Xie

Yue

et al. 2016

Molecular Carcinogenesis

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“…TGFBI has been observed to serve contradictory functions in tumorigenesis . Although TGFBI was reported to function as a tumour suppressor in leukaemia and ovarian, prostate, and lung carcinomas, the tumour‐promoting role of TGFBI was indicated in renal cell carcinoma, pancreatic carcinoma, oral and oesophageal squamous cell carcinoma, and colon carcinoma . Furthermore, Han et al reported a role for TGFBI in tumorigenesis of the gastrointestinal tract by demonstrating that TGFBI overexpression increased the incidence of spontaneous tumours including gastric adenocarcinoma in transgenic mice.…”

Section: Discussionmentioning

confidence: 99%

High stromal transforming growth factor β–induced expression is a novel marker of progression and poor prognosis in gastric cancer

Suzuki

Yokobori

Gombodorj

et al. 2018

Journal of Surgical Oncology

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“…The results of the meta-analysis conducted by Yang demonstrated that the high expression of TGF-β was strongly associated with the 3-year survival rate in patients with glioma [30]. Similar results were also found in patients with gastric cancer [31], hepatocellular carcinoma [32], renal cancer [33], breast cancer [34], and oesophageal cancer [35]. …”

Section: Discussionmentioning

confidence: 71%

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis

Chen

Zhu

et al. 2017

BMC Cancer

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BackgroundTransforming growth factor-beta (TGF-β) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-β can be used as a prognostic indicator of colorectal cancer (CRC) remains controversial.MethodsThe Medline, EMBASE and Cochrane databases were searched from their inception to March 2016. The studies that focused on TGF-β as a prognostic factor in patients with CRC were included in this analysis. Overall survival (OS) and disease-free survival (DFS) were analysed separately. A meta-analysis was performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated.ResultsTwelve studies were included in the analysis, of which 8 were used for OS and 7 for DFS. In all, 1622 patients with CRC undergoing surgery were included. Combined HRs suggested that high expression of TGF-β had a favourable impact on OS (HR = 1.68, 95% CI: 1.10–2.59) and DFS (HR = 1.11, 95% CI: 1.03–1.19) in CRC patients. For OS, the combined HRs of Asian studies and Western studies were 1.50 (95% CI: 0.61–3.68) and 1.80 (95% CI: 1.33–2.45), respectively. For DFS, the combined HRs of Asian studies and Western studies were 1.42 (95% CI: 0.61–3.31) and 1.11 (95% CI: 1.03–1.20), respectively.ConclusionsThis meta-analysis demonstrates that TGF-β can be used as a prognostic biomarker for CRC patients undergoing surgery, especially for CRC patients from Western countries.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3215-7) contains supplementary material, which is available to authorized users.

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TGFBI Expression in Cancer Stromal Cells is Associated with Poor Prognosis and Hematogenous Recurrence in Esophageal Squamous Cell Carcinoma

Abstract: High TGFBI expression in ESCC tissues could be a powerful biomarker of poor prognosis and hematogenous recurrence. TGFBI in stromal cells might be a promising molecular target for ESCC treatment.

Cited by 37 publications

References 24 publications

Cancer‐associated fibroblasts mediated chemoresistance by a FOXO1/TGFβ1 signaling loop in esophageal squamous cell carcinoma

Cancer‐associated fibroblasts mediated chemoresistance by a FOXO1/TGFβ1 signaling loop in esophageal squamous cell carcinoma

High stromal transforming growth factor β–induced expression is a novel marker of progression and poor prognosis in gastric cancer

Prognostic value of transforming growth factor-beta in patients with colorectal cancer who undergo surgery: a meta-analysis

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