Transforming growth factor-β in tumour development

Trelford, Charles B.; Dagnino, Lina; Guglielmo, Gianni M. Di

doi:10.3389/fmolb.2022.991612

Cited by 27 publications

(22 citation statements)

References 306 publications

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“…According to previous data, TGF-β is a known inducer of the EMT program [ 20 , 40 ]. Corroborating those findings, in our experimental model, the incubation of A549 cell line for 48 h incubation with this growth factor induced an increase in the percentage of snail + cells, from 19.85 ± 3.78 (mean ± SEM) in the control to 36.54 ± 6, 91 in the presence of TGF-β ( Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

“…The production of the growth factor TGF-β by the tumor microenvironment is one of the components capable of inducing EMT [ 20 ] via activation of several transcription factors that orchestrate the process: snail [ 21 ], slug [ 22 ], zeb1 [ 23 ] and twist-1 [ 24 ]. The reduction in the expression of E-cadherin, a calcium-dependent cell-cell adhesion protein expressed in epithelial cells, is very well known during EMT, being regulated by the aforementioned transcription factors, especially snail [ 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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ABCB1 and ABCC1 Function during TGF-β-Induced Epithelial-Mesenchymal Transition: Relationship between Multidrug Resistance and Tumor Progression

Costa

Freire-de-Lima

Fonseca

et al. 2023

IJMS

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Multidrug resistance (MDR) and induction of metastasis are some of the puzzles encountered during cancer chemotherapy. The MDR phenotype is associated with overexpression of ABC transporters, involved in drug efflux. Metastasis originates from the epithelial-mesenchymal transition (EMT), in which cells acquire a migratory phenotype, invading new tissues. ABC transporters’ role during EMT is still elusive, though cells undergoing EMT exhibit enhanced ABCB1 expression. We demonstrated increased ABCB1 expression but no change in activity after TGF-β-induced EMT in A549 cells. Moreover, ABCB1 inhibition by verapamil increased snail and fibronectin expression, an event associated with upregulation of ABCB1, evidencing coincident cell signaling pathways leading to ABCB1 and EMT-related markers transcription, rather than a direct effect of transport. Additionally, for the first time, increased ABCC1 expression and activity was observed after EMT, and use of ABCC1 inhibitors partially inhibited EMT-marker snail, although increased ABCC1 function translated into collateral sensibility to daunorubicin. More investigations must be done to evaluate the real benefits that the gain of ABC transporters might have on the process of metastasis. Considering ABCC1 is involved in the stress response, affecting intracellular GSH content and drug detoxification, this transporter could be used as a therapeutic target in cancer cells undergoing EMT.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ABCB1 and ABCC1 Function during TGF-β-Induced Epithelial-Mesenchymal Transition: Relationship between Multidrug Resistance and Tumor Progression

Costa

Freire-de-Lima

Fonseca

et al. 2023

IJMS

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“…Tsukada et al reported that PTX signi cantly suppressed transforming growth factor β (TGF-β)/Smad signaling in human peritoneal cells by inhibiting Smad2 phosphorylation and reducing stromal brosis in vitro [29]. The TGF-β/Smad pathway plays an important role in epithelialmesenchymal transition (EMT) [32,33], which is related to cancer progression and cancer-associated tissue brosis. This is thought to be a dual effect of paclitaxel, suppressing TGF-β and subsequently inhibiting cancer cell progression as a direct effect.…”

Section: Discussionmentioning

confidence: 99%

Impact of preoperative docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy on degree of malignant esophageal stenosis

Yamaguchi,

Okamoto,

Saito

et al. 2023

Preprint

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Background: Malignant esophageal stenosis is a common and severe complication of advanced esophageal cancer that can be a serious problem in the continuation of chemotherapy and other anticancer treatments. The impact of chemotherapy regimens on the degree of improvement in esophageal stenosis is unknown. In this study, we focused on the impacts of chemotherapy on the direct anticancer effects, and in the improvement of malignant stenosis. Methods: Patients who underwent radical esophagectomy after chemotherapy, either adjuvant 5-fluorouracil and cisplatin (FP) or docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen, were included. We assessed the length of the cancerous stenosis, the width of the narrowest segment, and the size of the intraluminal area in the stenotic segment, and compared the differences before and after chemotherapy. The antitumor effects of chemotherapy were also investigated. Results: A total of 81 patients were enrolled: 50 were treated with FP, and 31 were treated with DCF. The expansion rate in the length of the narrowest part was significantly increased in the DCF group compared with the FP group. Furthermore, the stenosis index (intraluminal stenotic area/stenotic length) was significantly increased in the DCF group compared with the FP group (112% vs 96%, P=0.038). The response rates were 60% in the FP group and 67.7% in the DCF group. Effective histopathological response (improvement to grade 2 or 3) was 24% in the FP group and 38.8% in the DCF group. Conclusion: DCF therapy is more effective than FP treatment in the improvement of malignant esophageal stenosis.

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“…In this regard, the treatment with T. cruzi antigens was associated with a decrease in splenic TGF-β levels, suggesting an attenuation of a regulatory immune response. In fact, TGF-β favours tumourigenesis, metastasis, angiogenesis, autophagy and immune suppression and can suppress antigen-presenting function of macrophages and dendritic cells [ 32 ]. Last, it would be worth exploring whether the immune response induced by the parasite antigens eliminates tumours, by rechallenging protected mice with tumour cells.…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

Freire

Landeira

Giacomini

et al. 2022

IJMS

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Lung cancer remains the leading cause of cancer mortality worldwide. Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice. We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate. Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-γ (IFN-γ) and tumour cell cytotoxicity. We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential.

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Transforming growth factor-β in tumour development

Cited by 27 publications

References 306 publications

ABCB1 and ABCC1 Function during TGF-β-Induced Epithelial-Mesenchymal Transition: Relationship between Multidrug Resistance and Tumor Progression

ABCB1 and ABCC1 Function during TGF-β-Induced Epithelial-Mesenchymal Transition: Relationship between Multidrug Resistance and Tumor Progression

Impact of preoperative docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy on degree of malignant esophageal stenosis

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

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