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CD146 as a potent target for anti-vascular therapies in lung cancer brain metastasis

ABSTRACT: To investigate the function of CD146 in the lung cancer brain metastasis cells, we established PC9-BrM3 cells in which CD146 has been knocked down by shRNA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE248935 | GEO | 2023/12/31

REPOSITORIES: GEO

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CD146 as a potent target for anti-vascular therapies in lung cancer brain metastasis

Project description:Tumors in brain are hype-angiogenic and the anti-vascular therapies are important for the treatment of non-small cell lung carcinoma (NSCLC) derived brain metastasis (BM). Targeting vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is the most effective way of resisting angiogenesis. However, the most widely-used anti-vascular drug (Bevacizumab, Bev) has limited therapeutic effects on NSCLC BM. Here, we defined the overexpression of CD146 and its potent pro-angiogenesis role in NSCLC BM in clinical samples, animal models and ex vivo bionic microfluidic chips. Mechanistically, CD146 exerts a comprehensive and sustained reinforcing effect on the pro-angiogenic VEGF-VEGFR2 axis on the one hand by up-regulating tumoral VEGF transcription and on the other hand by amplifying and sensitizing the VEGFR on endothelial cell as a co-receptor. By revealing the underlying mechanism by which CD146 upregulated in BM that the reactive astrocyte-derived growth arrest specific 6 (GAS6) induces the transcription of CD146 by activating AXL signaling, we demonstrated Bemcentinib (R428/BGB324), an AXL inhibitor, effectively suppressed the CD146 expression in BM cells and exhibited superior anti-vascular efficacy against brain metastases when used alone and in combination with Bev in vivo, providing novel anti-vascular strategies in BM.

2023-11-30 | PXD047390 | iProX

Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis

Project description:To investigate the function of AKR1B10 in the lung cancer brain metastasis cells, we established PC9-BrM3 cells in which AKR1B10 has been knocked down by shRNA.

2023-08-23 | GSE211215 | GEO

Reactive astrocytes promote tumor progression via up-regulating tumor PCDH1 expression in lung cancer brain metastasis

Project description:To investigate the function of PCDH1 in the lung cancer brain metastasis cells, we established PC9-BrM3 cells in which PCDH1 has been knocked down by shRNA.

2024-02-05 | GSE244170 | GEO

CD146 expression in mesenchymal stem cells is associated with vascular smooth muscle commitment

Project description:Bone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage. Clonal MSC were selected on the basis of CD146 level at their surface (CD146Low and CD146 High) and non-clonal MSC were compared from 4 different donors.

2013-07-04 | E-GEOD-48540 | biostudies-arrayexpress

CD146 expression in mesenchymal stem cells is associated with vascular smooth muscle commitment

2013-07-04 | GSE48540 | GEO

Comparative transcriptome of cancer cells with enhanced brain tropism

Project description:Comparative transcriptome analysis of WM266.4 versus WM266.4-BrM3 human melanoma cells and PC9 versus PC9-BrM4 human lung cancer cells

2020-05-15 | GSE150560 | GEO

The difference of gene expression signatures between CD146+ and CD146- cells in malignant rhabdoid tumor

Project description:To uncover the molecular mechanisms by which CD146+ malignant rhabdoid tumor cells exhibited higher tumorigenic potential, microarray analysis was carried out to compare gene expression profiles between CD146+ and CD146− cells isolated from three cell lines

2014-11-01 | GSE59025 | GEO

The difference of gene expression signatures between CD146+ and CD146- cells in malignant rhabdodid tumor

2014-11-01 | E-GEOD-59025 | biostudies-arrayexpress

Characterizing an HSF1-dependent transcriptional program in metastatic lung adenocarcinoma

Project description:The purpose of this study was to identify gene targets differentially regulated by shRNA-mediated knockdown of the HSF1 transcription factor in the brain-metastatic lung adenocarcinoma cell line PC9-BrM3.

2021-01-06 | GSE149246 | GEO

CD146 accelerates malignant progression of phyllodes tumor cells

Project description:Breast malignant phyllodes tumors (PTs) are rapid-progressing tumors, known to lack effective treatment and suitable prognostic markers as well as elaborate studies. Herein,we found that level of CD146 is progressively elevated with malignant progression of PTs and is an independent predictor for prognosis of PT patients.Mechanistically, CD146 activates the PI3K/AKT signaling pathway, thereby enhancing malignant behaviors of PT cells.This study unveils a CD146-PI3K/AKT axis in modulating the malignant progression of PTs, and open avenues to develop a novel target for precise prognosis and treatment for breast malignant PTs.

2023-12-01 | GSE227380 | GEO

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