Cancer-associated fibroblasts promote cell proliferation and invasion via paracrine Wnt/IL1β signaling pathway in human bladder cancer

Yang, Fan; Guo, Zhuifeng; He, Chang; Qi, Liang; Wang, Hang; Wu, Jiawen; Lu, Xuwei

doi:10.4149/neo_2020_200202n101

Cited by 19 publications

(12 citation statements)

References 13 publications

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“…For the control cells, the increase ranges from 16% (for the 1:10 ratio) to 35% (for the 1:5 ratio), for the cells dosed with GNPs it ranges from 20% (for the 1:10) to 33% (for the 1:5), for the irradiated cells it ranges from 8% (for the 1:10) to 23% (for the 1:5), and for the irradiated/GNP dosed cells it ranges from 6% (for the 1:10) to 20% (for the 1:5). The reason behind that is that CAFs not only encourage radioresistance but also promote cancer cell growth through paracrine signals [ 55 , 66 , 67 , 68 , 69 ]. Interestingly, Yang et al found a substantial decrease in cell proliferation of natural killer cells when co-cultured with irradiated or non-irradiated CAFs vs. when co-cultured with normal fibroblasts [ 55 ].…”

Section: Resultsmentioning

confidence: 99%

Potential of Gold Nanoparticles in Current Radiotherapy Using a Co-Culture Model of Cancer Cells and Cancer Associated Fibroblasts

Alhussan

Palmerley

Smazynski³

et al. 2022

Cancers

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Many cancer therapeutics are tested in vitro using only tumour cells. However, the tumour promoting effect of cancer associated fibroblasts (CAFs) within the tumour microenvironment (TME) is thought to reduce cancer therapeutics’ efficacy. We have chosen pancreatic ductal adenocarcinoma (PDAC) as our tumor model. Our goal is to create a co-culture of CAFs and tumour cells to model the interaction between cancer and stromal cells in the TME and allow for better testing of therapeutic combinations. To test the proposed co-culture model, a gold nanoparticle (GNP) mediated-radiation response was used. Cells were grown in co-culture with different ratios of CAFs to cancer cells. MIA PaCa-2 was used as our PDAC cancer cell line. Co-cultured cells were treated with 2 Gy of radiation following GNP incubation. DNA damage and cell proliferation were examined to assess the combined effect of radiation and GNPs. Cancer cells in co-culture exhibited up to a 23% decrease in DNA double strand breaks (DSB) and up to a 35% increase in proliferation compared to monocultures. GNP/Radiotherapy (RT) induced up to a 25% increase in DNA DSBs and up to a 15% decrease in proliferation compared to RT alone in both monocultured and co-cultured cells. The observed resistance in the co-culture system may be attributed to the role of CAFs in supporting cancer cells. Moreover, we were able to reduce the activity of CAFs using GNPs during radiation treatment. Indeed, CAFs internalize a significantly higher number of GNPs, which may have led to the reduction in their activity. One reason experimental therapeutics fail in clinical trials relates to limitations in the pre-clinical models that lack a true representation of the TME. We have demonstrated a co-culture platform to test GNP/RT in a clinically relevant environment.

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Section: Resultsmentioning

confidence: 99%

Potential of Gold Nanoparticles in Current Radiotherapy Using a Co-Culture Model of Cancer Cells and Cancer Associated Fibroblasts

Alhussan

Palmerley

Smazynski³

et al. 2022

Cancers

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“…Similar to our Tg-Twist1 iEC+ mice, overactivation of Wnt/β-catenin signaling by Ctnna1 mutation can lead to defective retinal angiogenesis, including slower vascular progression, increased EC proliferation, and greater pathological NV ( Zhu et al, 2021 ). Overactivation of Wnt/β-catenin signaling can promote cell proliferation and is well established in multiple cell types ( Li et al, 2020 ; Yang et al, 2021 ). Why did the progression of retinal vasculature from the optic nerve to the peripheral retina seem slowed under the condition of TWIST1 promotes EC proliferation?…”

Section: Discussionmentioning

confidence: 99%

Overexpression of <i>Twist1</i> in vascular endothelial cells promotes pathological retinal angiogenesis in mice

Zhang

Wang

et al. 2022

Zoological Research

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Retinal angiogenesis is a critical process for normal retinal function. However, uncontrolled angiogenesis can lead to pathological neovascularization (NV), which is closely related to most irreversible blindness-causing retinal diseases. Understanding the molecular basis behind pathological NV is important for the treatment of related diseases. Twist-related protein 1 (TWIST1) is a well-known transcription factor and principal inducer of epithelial-mesenchymal transition (EMT) in many human cancers. Our previous study showed that Twist1 expression is elevated in pathological retinal NV. To date, however, the role of TWIST1 in retinal pathological angiogenesis remains to be elucidated. To study the role of TWIST1 in pathological retinal NV and identify specific molecular targets for antagonizing pathological NV, we generated an inducible vascular endothelial cell (EC)-specific Twist1 transgenic mouse model ( Tg-Twist1 iEC+ ). Whole-mount retinas from Tg-Twist1 iEC+ mice showed retarded vascular progression and increased vascular density in the front end of the growing retinal vasculature, as well as aneurysm-like pathological retinal NV. Furthermore, overexpression of Twist1 in the ECs promoted cell proliferation but disturbed cell polarity, thus leading to uncontrolled retinal angiogenesis. TWIST1 promoted pathological NV by activating the Wnt/β-catenin signaling pathway and inducing the expression of NV formation-related genes, thereby acting as a ‘valve’ in the regulation of pathological angiogenesis. This study identified the critical role of TWIST1 in retinal pathological NV, thus providing a potential therapeutic target for pathological NV.

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“…Telomerase reverse transcriptase has become an important target for the diagnosis and treatment of human tumours [ 38 , 39 ]. Activation of the hTERT gene is strictly regulated by a variety of signalling pathways in different human tumours, specifically the Wnt/β-catenin, NF-κB and c-Myc signalling pathways [ 10 , 13 , 28 , 40 , 41 ]. However, during ALV-J-induced tumorigenesis, the molecular mechanism by which the chTERT gene regulates the Wnt/β-catenin signalling pathway and participates in cell growth and virus replication is still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…The significance of this pathway is exemplified by evidence that both the overexpression and underexpression of target genes involved in this pathway result in various diseases. Appropriate regulation of the Wnt/β-catenin signalling pathway is key for cells to carry out their normal functions [ 28 , 30 ]. The Wnt/β-catenin signalling pathway has been implicated in the transcriptional reactivation of hTERT in cancer cells; transient activation of Wnt/β-catenin induces hTERT mRNA expression and elevates telomerase activity in different cell lines [ 12 , 31 – 33 ].…”

Section: Introductionmentioning

confidence: 99%

Mutual regulation between chicken telomerase reverse transcriptase and the Wnt/β-catenin signalling pathway inhibits apoptosis and promotes the replication of ALV-J in LMH cells

Xiang

et al. 2021

Vet Res

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This study aimed to explore the mutual regulation between chicken telomerase reverse transcriptase (chTERT) and the Wnt/β-catenin signalling pathway and its effects on cell growth and avian leukosis virus subgroup J (ALV-J) replication in LMH cells. First, LMH cells stably overexpressing the chTERT gene (LMH-chTERT cells) and corresponding control cells (LMH-NC cells) were successfully constructed with a lentiviral vector expression system. The results showed that chTERT upregulated the expression of β-catenin, Cyclin D1, TCF4 and c-Myc. chTERT expression level and telomerase activity were increased when cells were treated with LiCl. When the cells were treated with ICG001 or IWP-2, the activity of the Wnt/β-catenin signalling pathway was significantly inhibited, and chTERT expression and telomerase activity were also inhibited. However, when the β-catenin gene was knocked down by small interfering RNA (siRNA), the changes in chTERT expression and telomerase activity were consistent with those in cells treated with ICG001 or IWP-2. These results indicated that chTERT and the Wnt/β-catenin signalling pathway can be mutually regulated. Subsequently, we found that chTERT not only shortened the cell cycle to promote proliferation but also inhibited apoptosis by downregulating the expression of Caspase 3, Caspase 9 and BAX; upregulating BCL-2 and BCL-X expression; and promoting autophagy. Moreover, chTERT significantly enhanced the migration ability of LMH cells, upregulated the protein and mRNA expression of ALV-J and increased the virus titre. ALV-J replication promoted chTERT expression and telomerase activity.

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Cancer-associated fibroblasts promote cell proliferation and invasion via paracrine Wnt/IL1β signaling pathway in human bladder cancer

Cited by 19 publications

References 13 publications

Potential of Gold Nanoparticles in Current Radiotherapy Using a Co-Culture Model of Cancer Cells and Cancer Associated Fibroblasts

Potential of Gold Nanoparticles in Current Radiotherapy Using a Co-Culture Model of Cancer Cells and Cancer Associated Fibroblasts

Overexpression of <i>Twist1</i> in vascular endothelial cells promotes pathological retinal angiogenesis in mice

Mutual regulation between chicken telomerase reverse transcriptase and the Wnt/β-catenin signalling pathway inhibits apoptosis and promotes the replication of ALV-J in LMH cells

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