Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARγ signalling pathway

Lee, Jungwhoi; Lee, Jungsul; Sim, Woogwang; Kim, Jae-Hoon

doi:10.1007/s13402-022-00668-7

Cited by 15 publications

(6 citation statements)

References 46 publications

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“…Its primary role consists in connecting various integrins to the ECM. However, a growing body of research points towards its two-edged role in regulating tumor progression and resistance [71] , [72] . Central to radio(chemo)therapy was the discovery that TGFBI mediates a survival advantage by modifying DNA damage repair [73] .…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types – A one research lab re-evaluation

Borodins¹,

Broghammer²,

Seifert³

et al. 2023

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types – A one research lab re-evaluation

Borodins¹,

Broghammer²,

Seifert³

et al. 2023

Computational and Structural Biotechnology Journal

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“…CCArly CAFs were the main source of secreted TNC and MMP2. Increased MMP2 and TGFBI levels had previously been associated with poor prognosis in CCA [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

MUG CCArly: A Novel Autologous 3D Cholangiocarcinoma Model Presents an Increased Angiogenic Potential

Schrom

Kleinegger

Anders

et al. 2023

Cancers

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Cholangiocarcinoma (CCA) are characterized by their desmoplastic and hypervascularized tumor microenvironment (TME), which is mainly composed of tumor cells and cancer-associated fibroblasts (CAFs). CAFs play a pivotal role in general and CCA tumor progression, angiogenesis, metastasis, and the development of treatment resistance. To our knowledge, no continuous human in vivo-like co-culture model is available for research. Therefore, we aimed to establish a new model system (called MUG CCArly) that mimics the desmoplastic microenvironment typically seen in CCA. Proteomic data comparing the new CCA tumor cell line with our co-culture tumor model (CCTM) indicated a higher gene expression correlation of the CCTM with physiological CCA characteristics. A pro-angiogenic TME that is typically observed in CCA could also be better simulated in the CCTM group. Further analysis of secreted proteins revealed CAFs to be the main source of these angiogenic factors. Our CCTM MUG CCArly represents a new, reproducible, and easy-to-handle 3D CCA model for preclinical studies focusing on CCA-stromal crosstalk, tumor angiogenesis, and invasion, as well as the immunosuppressive microenvironment and the involvement of CAFs in the way that drug resistance develops.

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“…Transforming growth factor beta induced (TGFBI) exacerbates the malignancy of CHOL cells in vitro and in vivo by activating the integrin beta-1 (ITGB1)-dependent peroxisome proliferator-activated receptor gamma signaling pathway, and its high expression is also associated with poor prognosis in patients with BTCs (40)(41)(42). Furthermore, our study demonstrated that high CXCL12 expression was prevalent in the CAFs of BTCs and bound to ITGB1 receptors on the surface of tumor cells, revealing a regulatory role of ITGB1 on BTCs at the single-cell level.…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis reveals heterogeneity in the molecular profile of the tumor microenvironment of biliary tract cancers

Lai,

Mai,

Tsauo

et al. 2023

Preprint

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Background Biliary tract cancers (BTCs) are heterogeneous malignancies with diverse tumor microenvironment (TME) cells that contribute to tumor progression. However, the characteristics of the TME among different subtypes of BTCs remain unclear. Methods We integrated single-cell RNA sequencing data from BTC patients (iCCA, GBC, and eCCA) and RNA sequencing data from cholangiocarcinoma samples to construct a cellular molecular atlas of BTCs. Through enrichment analysis, we explored signaling pathways in tumor and TME cells, identified developmental trajectories and characterized transcription factors regulating different cell subpopulations using pseudotime analysis and gene regulatory network analysis. Moreover, we analyzed the intercellular communication between tumor cells and TME cells in different BTCs and developed a prognostic model. Results Malignant cells in different BTCs displayed significant heterogeneity, with variations in immune cell composition, biological functions, and metabolic pathways. Notably, the iCCA subpopulation demonstrated enhanced invasive potential, while the eCCA and GBC subpopulations showed significant activation of energy metabolism-related pathways. The carcinoma-associated fibroblast subpopulations in eCCA and GBC may regulate tumor cell metabolism through metabolic reprogramming, thereby facilitating tumor proliferation. GBC specifically exhibited enrichment of CXCL13 + tumor-reactive CD8 + T cells, indicating a potentially favorable response to immune checkpoint blockade therapy. Additionally, as tumor progression occurred, macrophage subpopulations in all three BTCs displayed M1/M2 dichotomous polarization, and the antigen-presenting ability of monocyte-derived dendritic cells gradually decreased. Conclusion This study analyzed single-cell landscape heterogeneity across BTC subtypes, revealing complex intercellular communication within the TME. A prognostic model was developed, providing insights for personalized precision medicine.

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Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARγ signalling pathway

Cited by 15 publications

References 46 publications

Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types – A one research lab re-evaluation

Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types – A one research lab re-evaluation

MUG CCArly: A Novel Autologous 3D Cholangiocarcinoma Model Presents an Increased Angiogenic Potential

Single-cell analysis reveals heterogeneity in the molecular profile of the tumor microenvironment of biliary tract cancers

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