TY - JOUR
T1 - The role of transforming growth factor β in upper gastrointestinal cancers
T2 - A systematic review
AU - Veen, Linde M.
AU - Skrabanja, Tim L.P.
AU - Derks, Sarah
AU - de Gruijl, Tanja D.
AU - Bijlsma, Maarten F.
AU - van Laarhoven, Hanneke W.M.
N1 - Funding Information: TdG has an advisory role at DCPrime BV and received research funding from Idera Pharmaceuticals. MB acted as a consultant to Servier. HvL has an advisory role at BMS, Lilly, MSD, Nordic Pharma, Bayer and Servier. HvL also received research funding from Bayer, BMS, Lilly, Nordic Pharma and Servier. None of these parties were involved in drafting this manuscript or the study design. The other authors declare no competing interests. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The transforming growth factor β (TGF-β) pathway might play a role in the development of treatment resistance. In this systematic review, we provide an overview of preclinical studies investigating the role of TGF-β in esophageal and gastric malignancies. We systematically searched MEDLINE/PubMed and EMBASE for eligible preclinical studies describing the effect of TGF-β or TGF-β inhibition on hallmarks of cancer, such as proliferation, migration, invasion, angiogenesis and immune evasion. In total, 2107 records were screened and 45 articles were included, using mouse models and 45 different cell lines. TGF-β failed to induce apoptosis in twelve of sixteen tested cell lines. TGF-β could either decrease (five cell lines) or increase proliferation (seven cell lines) in gastric cancer cells, but had no effect in esophageal cancer cells. In all esophageal and all but two gastric cancer cell lines, TGF-β increased migratory, adhesive and invasive capacities. In vivo studies showed increased metastasis in response to TGF-β treatment. Additionally, TGF-β was shown to induce vascular endothelial growth factor production and differentiation of cancer-associated fibroblasts and regulatory T-cells. In conclusion, we found that TGF-β enhances hallmarks of cancer in most gastric and esophageal cancer cell lines, but not in all. Therefore, targeting the TGF-β pathway could be an attractive strategy in patients with gastric or esophageal cancer, but additional clinical trials are needed to define patient groups who would benefit most.
AB - Esophageal and gastric malignancies are associated with poor prognosis, in part due to development of recurrences or metastases after curative treatment. The transforming growth factor β (TGF-β) pathway might play a role in the development of treatment resistance. In this systematic review, we provide an overview of preclinical studies investigating the role of TGF-β in esophageal and gastric malignancies. We systematically searched MEDLINE/PubMed and EMBASE for eligible preclinical studies describing the effect of TGF-β or TGF-β inhibition on hallmarks of cancer, such as proliferation, migration, invasion, angiogenesis and immune evasion. In total, 2107 records were screened and 45 articles were included, using mouse models and 45 different cell lines. TGF-β failed to induce apoptosis in twelve of sixteen tested cell lines. TGF-β could either decrease (five cell lines) or increase proliferation (seven cell lines) in gastric cancer cells, but had no effect in esophageal cancer cells. In all esophageal and all but two gastric cancer cell lines, TGF-β increased migratory, adhesive and invasive capacities. In vivo studies showed increased metastasis in response to TGF-β treatment. Additionally, TGF-β was shown to induce vascular endothelial growth factor production and differentiation of cancer-associated fibroblasts and regulatory T-cells. In conclusion, we found that TGF-β enhances hallmarks of cancer in most gastric and esophageal cancer cell lines, but not in all. Therefore, targeting the TGF-β pathway could be an attractive strategy in patients with gastric or esophageal cancer, but additional clinical trials are needed to define patient groups who would benefit most.
KW - Esophageal carcinoma
KW - Gastric carcinoma
KW - Systematic review
KW - TGF-β
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85114942784&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ctrv.2021.102285
DO - https://doi.org/10.1016/j.ctrv.2021.102285
M3 - Review article
C2 - 34536730
SN - 0305-7372
VL - 100
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
M1 - 102285
ER -