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Characterization of cancer-associated fibroblasts from ex vivo germ cell tumors

ABSTRACT: Cancer-associated fibroblasts (CAF) as one abundant cell type of the tumor microenvironment are known to have tumor supporting abilities by promoting tumor proliferation and modulating the immunal landscape. In this study, germ cell tumor-derived CAF were molecular and epigenetically characterized to identify CAF secreted signal molecules which play a pivotal role in the GCT-CAF interaction.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Seminoma,Teratoma,Germ Cell Cancer,Embryonal Carcinoma

SUBMITTER: Gereon Poschmann

LAB HEAD: Gereon Poschmann

PROVIDER: PXD049249 | Pride | 2024-11-15

REPOSITORIES: Pride

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			Action	DRS
	CAF_quant_files.zip	Other
	CAF_search_results.zip	Other
	CAF_spectral_library.zip	Other
	LM05725.raw	Raw
	LM05726.raw	Raw

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Publications

Molecular and epigenetic ex vivo profiling of testis cancer-associated fibroblasts and their interaction with germ cell tumor cells and macrophages.

Stephan Alexa A Suhrmann Jan-Henrik JH Skowron Margaretha A MA Che Yue Y Poschmann Gereon G Petzsch Patrick P Kresbach Catena C Wruck Wasco W Pongratanakul Pailin P Adjaye James J Stühler Kai K Köhrer Karl K Schüller Ulrich U Nettersheim Daniel D

Matrix biology : journal of the International Society for Matrix Biology 20240606

Germ cell tumors (GCT) are the most common solid tumors in young men of age 15 - 40. In previous studies, we profiled the interaction of GCT cells with cells of the tumor microenvironment (TM), which showed that especially the 3D interaction of fibroblasts (FB) or macrophages with GCT cells influenced the growth behavior and cisplatin response as well as the transcriptome and secretome of the tumor cells, suggesting that the crosstalk of these cells with GCT cells is crucial for tumor progressio ...[more]

PMID: 38851302

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RNA sequencing data of primary cancer-associated fibroblasts (CAF) isolated from fresh ex vivo germ cell tumor (GCT) patient tissue

Project description:Single eng 3' RNA sequencing of primary CAF isolated from fresh ex vivo GCT patient tissue. Purity of CAF populations were verified by qPCR analysis of common CAF, GCT, endothelial and epithelial markers. 14 different CAF cultures from distinct GCT subtypes (seminoma(SE), non-seminoma(NS)) and 5 non-malignant fibroblast cultures were analyzed.

2024-06-21 | GSE229047 | GEO

Illumina Infinium MethylationEPIC BeadChip (850k) data of primary cancer-associated fibroblasts (CAF) isolated from fresh ex vivo germ cell tumor (GCT) patient tissue

Project description:Illumina Infinium MethylationEPIC BeadChip (850k) array analysis of DNA methylation of primary CAF isolated from fresh ex vivo GCT patient tissue. Purity of CAF populations were verified by qPCR analysis of common CAF, GCT, endothelial and epithelial markers. 14 different CAF cultures from distinct GCT subtypes (seminoma(SE), non-seminoma(NS)) and 5 non-malignant fibroblast cultures were analyzed.

2024-06-21 | GSE228405 | GEO

Proteomic profiling of extracellular vesicles from cancer-associated fibroblast-induced myeloid-derived suppressor cells and related cell types

Project description:Cancer-associated fibroblast (CAF) promote immune suppression in the tumor microenvironment by polarizing monocytes to myeloid-derived suppressor cells (MDSC) that potently suppress T-cell function. Using a patient-derived coculture system, we found that extracellular vesicles (EV) released by CAF-induced MDSC directly suppress T-cell proliferation. In this study, we profiled the protein cargo of the EVs isolated from CAF-MDSC and compared to related cell types.

2024-01-03 | PXD035248 | Pride

Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature

Project description:Tumor growth and metastasis is controlled by paracrine signaling between cells of the tumor microenvironment and malignant cells. Cancer-associated fibroblasts (CAFs), are functionally important components of the tumor microenvironment. Although some steps involved in the cross-talk between these cells are known, there is still a lot that is not clear. Thus, the addition of, the consideration of microenvironment in the development of the disease, to the clinical and pathological procedures (currently admitted as the consistent value cancer treatments) could lay the foundations for the development of new treatment strategies to control the disease. Primary CAF cultures from 15 primary human colon tumors were established Their purity was evaluated by the expression of various epithelial and myofibroblast specific markers Co-culture assays of primary CAFs with different colon tumor cells were performed to evaluate pro-migratory CAF-derived effects on cancer cells CAF gene expression profiles were analyzed by microarray to identify deregulated genes in different pro-migratory CAFs

2013-10-30 | E-GEOD-51257 | biostudies-arrayexpress

Cell surface proteome profiling of cancer-associated fibroblast-induced myeloid-derived suppressor cells and related cell types

Project description:Cancer-associated fibroblasts (CAF) promote immune suppression in the tumor microenvironment by polarizing monocytes to myeloid-derived suppressor cells (MDSC) that potently suppress T-cell function. Using a patient-derived coculture system, we profiled the cell surface proteome of CAF-induced MDSC to identify potential mechanism through which T-cell function is impaired.

2024-01-03 | PXD035259 | Pride

Carcinoma-associated fibroblasts’ transcriptomic program predicts clinical outcome in stage II/III colorectal cancer

Project description:We obtained fibroblast cultures from fresh surgical specimen ressected from patients with primary colorectal carcinoma: normal colonic fibroblasts (NCF=9) from the normal colonic mucosa at least 5-10cm from the surgical margin, carcinoma-associated fibroblasts from the primary tumor (CAF-PT=14) and carcinoma-associated fibroblasts (CAF-LM=11) from fresh surgical specimens of liver metastases. We identified 277 probes, in common between the three types of fibroblasts, whose expression level is sequentially deregulated according to cancer progression (NCF→CAF-PT→CAF-LM; fold change Log2 normalized expression>1.5 in each step). Prediction Analysis of Microarrays was applied to obtain a 25-gene signature that better characterizes each fibroblast class. The signature is able to classify patients carrying primary tumors according to prognosis. This fact was exploited to obtain a 19-gene signature (from the 277 deregulated probes) predicting recurrence with high accuracy in stage II/III colorectal cancer patients. Signature validation has been carried out in two independent datasets and in a meta-cohort of 336 stage II/III patients. Since the 25-gene signature was obtained regardless of gene expression data of tumor specimens or patient’s clinical data, the prognostic power of this signature provides strong evidence of the link between the tumor stroma and cancer progression. Furthermore, the 19-gene signature was able to identify low-risk patients with very high accuracy, especially relevant for those high-risk stage-II patients. We hybridised fibroblast RNA in Affymetrix GeneChip 1.0 st arrays

2013-05-10 | E-GEOD-46824 | biostudies-arrayexpress

Proteomic analysis Carcinoma associated fibroblasts (CAFs) following genetic manipulation of NID2 expression

Project description:Proteomic anlaysis was performed on CAF GFP-1 KRAB, CAF B500 NID2 KRAB and CAF C500 NID2 KRAB cell lines

2024-08-10 | PXD050045 | Pride

Human carcinoma-associated fibroblasts (CAF): co-culture with cancer cells vs. CAF only

Project description:Gene expression profiling of CAF co-cultured with human oral squamous cell carcinoma (OSCC) cells compared with mono-cultured CAF. To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing co-cultured OSCC cells and CAF with monoculture controls. comparison 1: CAF co-cultured with OSCC vs. mono-cultured CAF comparison 2: OSCC co-cultured with CAF vs. mono-cultured OSCC 1.7X10(5) YD-10B OSCC cells and 1.7X10(5) CAF were seeded in the upper chamber and lower chamber, respectively, of 6-transwell plates containing collagen-coated 1 micrometer pore transmembrane filters (Becton Dickinson, Franklin Lakes, NJ, USA). Monoculture control samples were generated by culturing only CAF or OSCC on the same side of the filter as in the co-culture design.

2010-06-21 | E-GEOD-18532 | biostudies-arrayexpress

Proteomic profiling of human prostate cancer-associated fibroblasts identifies LOXL2 promotes tumour migration in the extracellular matrix

Project description:In prostate cancer (PC), cancer-associated fibroblasts (CAFs) exhibit contrasting biological properties to non-malignant prostate fibroblasts (NPFs) and promote tumorigenesis. Resolving intercellular signaling pathways between CAFs and prostate tumor epithelium may offer novel opportunities for research translation. To this end, the proteome and phosphoproteome of four pairs of patient-matched CAFs and NPFs were characterized to identify discriminating proteomic signatures. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a hyper-reaction monitoring data-independent acquisition (HRM-DIA) workflow. Proteins that exhibited a significant increase in CAFs versus NPFs were enriched for the functional categories ‘cell adhesion’ and the ‘extracellular matrix’. The CAF phosphoproteome exhibited enhanced phosphorylation of proteins associated with the ‘spliceosome’ and ‘actin binding’. STRING analysis of the CAF proteome revealed a prominent interaction hub associated with collagen synthesis, modification, and signaling. It contained multiple collagens, including the fibrillar types COL1A1/2 and COL5A1; the receptor tyrosine kinase discoidin domain-containing receptor 2 (DDR2), a receptor for fibrillar collagens; and lysyl oxidase-like 2 (LOXL2), which promotes collagen crosslinking. Increased activity and/or expression of LOXL2 and DDR2 in CAFs were confirmed by enzymatic assays and Western blot analyses. Pharmacological inhibition of CAF-derived LOXL2 perturbed extracellular matrix (ECM) organization and decreased cell migration in wound-healing assays. Furthermore, it significantly impaired the motility of co-cultured RWPE2 prostate tumor epithelial cells. These results indicate that CAF-derived LOXL2 is an important mediator of intercellular communication within the PC tumor microenvironment and a potential therapeutic target.

2019-05-24 | PXD010611 | Pride

A novel 3-D organotypic culture model by co-culturing alpha-SMA positive CAF and cholangiocarcinoma cells in a collagen matrix

Project description:The increased M-NM-1-smooth muscle-actin positive cancer-associated fibroblastic cells (CAF) in the desmoplastic stroma may relate to a more aggressive cancer and worse survival outcomes for intrahepatic cholangiocarcinoma (ICC) patients We developed a novel 3-D organotypic culture model by co-culturing M-NM-1-SMA positive CAF and cholangiocarcinoma cells in a collagen matrix. Cholangiocarcinoma cell lines were established by isolating M-NM-1-SMA positive cancer-associated fibroblastic cells (CAF) (BDEsp-TDFE4) and cholangiocarcinoma cells (BDEsp-TDEH10) from tumors arising from bile duct inoculation of spontaneously-transformed low grade malignant rat BDE1 cholangiocytes (BDEsp cells). These tumor-derived cells lines were then grown in a rat tail type I collagen gel matrix, alone or in co-culture, and their gene expression profile were compared.

2012-06-22 | E-GEOD-38889 | biostudies-arrayexpress