Mass spectrometry results of LDHB knockout fibroblast cell lysates from breast cancer patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Wenhua Li
PROVIDER: PXD055370 | iProX | Thu Oct 09 00:00:00 BST 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Intratumoral hypoxia causes the formation of dysfunctional blood vessels which contribute to tumor metastasis. Blood vessels are embedded in the tumor stroma where cancer-associated fibroblasts (CAFs) constitute the most prominent cellular component. We found that hypoxic human mammary CAFs promote blood vessel growth in CAF-endothelial cell co-cultures in vitro. Mass spectrometry-based proteomic analysis of CAF secretome unravels how hypoxic CAFs contribute to blood vessel abnormalities by altering the secretion of a multitude of pro- and anti-angiogenic factors. Hypoxia induces pronounced remodeling of the CAF proteome, including proteins that have not been previously related to this process. Our study provides a map of unprecedented depth of hypoxia-induced molecular alterations in mammary CAFs that can be exploited to identify novel mechanisms that control hypoxic CAF functions.
2019-02-15 | PXD006535 | Pride
Project description:Intratumoral hypoxia causes the formation of dysfunctional blood vessels which contribute to tumor metastasis. Blood vessels are embedded in the tumor stroma where cancer-associated fibroblasts (CAFs) constitute the most prominent cellular component. We found that hypoxic human mammary CAFs promote blood vessel growth in CAF-endothelial cell co-cultures in vitro. Mass spectrometry-based proteomic analysis of CAF secretome unravels how hypoxic CAFs contribute to blood vessel abnormalities by altering the secretion of a multitude of pro- and anti-angiogenic factors. Hypoxia induces pronounced remodeling of the CAF proteome, including proteins that have not been previously related to this process. Amongst those, the uncharacterized antisense gene protein NCBP2-AS2 is one of the most transcriptionally upregulated proteins in the proteome and secretome of hypoxic CAFs. Silencing of NCBP2-AS2 abrogates the pro-angiogenic function acquired by hypoxic CAFs through decreasing VEGF expression levels to the levels found in normoxic CAFs.
2019-02-15 | PXD006539 | Pride
Project description:A greater understanding of cell signaling events that occur within the prostate cancer tumor microenvironment (TME), for example between cancer-associated fibroblasts (CAFs) and prostate epithelial or cancer cells, may identify novel biomarkers and more effective therapeutic strategies for this disease. To address this, we used cell-type specific labelling with amino acid precursors (CTAP) to define cell type-specific phosphoproteomic changes that occur when prostate epithelial cells are co-cultured with normal patient-derived prostate fibroblasts (NPFs) versus matched CAFs.
2023-03-11 | PXD037272 | Pride
Project description:The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo transition at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα+IL-1β (2-3 weeks) gained a CAF-like morphology, accompanied by prominent changes in gene expression, including in stroma/fibroblast-related genes. These CAF-like cells expressed elevated levels of vimentin and fibroblast activation protein (FAP) and demonstrated significantly increased ability to contract collagen gels. Moreover, they have gained the phenotype of inflammatory CAFs, as indicated by reduced expression of α smooth muscle actin (αSMA), increased proliferation and elevated expression of inflammatory genes and proteins, primarily inflammatory chemokines. These inflammatory CAFs released factors that enhanced tumor cell detachment, spreading and migration; the inflammatory CAF-derived factors elevated cancer cell migration by stimulating the chemokine receptors CCR2, CCR5 and CXCR1/2 and Ras-activating receptors, expressed by the cancer cells. Together, these novel findings demonstrate that chronic inflammation, per se, can induce MSC-to-CAF transition, leading to generation of tumor-promoting inflammatory CAFs.
2021-08-10 | PXD022635 | Pride
Project description:Cancer-associated fibroblasts (CAFs) are an integral part of the tumor microenvironment often linked to drug resistance. Here, we report that CAFs, but not normal fibroblasts, can promote either resistance or unexpected drug sensitization of different lung cancer cells. Using unbiased secretomics, transcriptomics and tyrosine phosphoproteomics, we observed differential expression of several IGF1R signaling components, such as IGF-binding proteins and IGF1/2, and downstream signaling effects on cancer cells by fibroblasts. IGF1/2 treatment or IGFBP5 silencing in CAFs reversed, while addition of exogenous IGFBPs or pharmacological IGF1R inhibitors phenocopied the sensitizing effects. Combining IGF1R and EGFR inhibitors synergized in 2D and 3D models of different drug-resistant and naïve EGFR-mutant lung cancer cells and decreased tumor growth in vivo. These results suggest that multiple resistance mechanisms coexist within the same cancer cells, that CAFs context-dependently cause drug resistance or sensitization, and that understanding both of these differential mechanisms leads to improved therapeutic approaches.
2023-03-11 | PXD023626 | Pride
Project description:Cancer-associated fibroblasts (CAFs) are an integral part of the tumor microenvironment often linked to drug resistance. Here, we report that CAFs, but not normal fibroblasts, can promote either resistance or unexpected drug sensitization of different lung cancer cells. Using unbiased secretomics, transcriptomics and tyrosine phosphoproteomics, we observed differential expression of several IGF1R signaling components, such as IGF-binding proteins and IGF1/2, and downstream signaling effects on cancer cells by fibroblasts. IGF1/2 treatment or IGFBP5 silencing in CAFs reversed, while addition of exogenous IGFBPs or pharmacological IGF1R inhibitors phenocopied the sensitizing effects. Combining IGF1R and EGFR inhibitors synergized in 2D and 3D models of different drug-resistant and naïve EGFR-mutant lung cancer cells and decreased tumor growth in vivo. These results suggest that multiple resistance mechanisms coexist within the same cancer cells, that CAFs context-dependently cause drug resistance or sensitization, and that understanding both of these differential mechanisms leads to improved therapeutic approaches.
2023-03-11 | PXD023692 | Pride
Project description:Pancreatic stellate cells are thought to be the predominant source of cancer-associated fibroblasts (CAFs) in pancreatic cancer. We developed a mouse model which allows us to track and analyze stellate cells and stellate cell-derived CAFs in vivo during pancreatic tumorigenesis for the first time. We find that stellate cells in fact give rise to a minority of all CAFs. Here, we have used lineage reporters to isolate stellate cell-derived and non-stellate cell-derived CAFs and compared them by RNA-seq.
2021-09-16 | GSE143805 | GEO
Project description:Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF?-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF?-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF?-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. In the present study, patient derived-CAFs and HPFs activated in vitro with either TGF? or IL6 were comparatively analyzed for gene and microRNA (miRNA) expression profiles, with the aim to define transcriptional pathways responsible for fibroblast activation and establish whether different subpopulations of CAFs may exist in PCa.
2015-09-01 | E-GEOD-68164 | biostudies-arrayexpress
Project description:Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGFβ-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGFβ-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGFβ-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. In the present study, patient derived-CAFs and HPFs activated in vitro with either TGFβ or IL6 were comparatively analyzed for gene and microRNA (miRNA) expression profiles, with the aim to define transcriptional pathways responsible for fibroblast activation and establish whether different subpopulations of CAFs may exist in PCa.
2015-09-01 | E-GEOD-68165 | biostudies-arrayexpress
Project description:The tumor microenvironment strongly influences cancer development, progression and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-beta signaling pathway. We have identified a subset of 11 genes that formed a prognostic gene expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene expression changes revealed prominent involvement of the focal adhesion and MAPK signalling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture micro-dissected corresponding primary tumor stroma compared to the matched normal lung. Six of these 14 genes could be induced by TGF-beta1 in NF. The results establish the prognostic impact of CAF-associated gene expression changes in NSCLC patients. Methylation profiles of 5 pairs of were included in a molecular characterization of NSCLC fibroblast cell lines (CAFs) vs. normal lung fibroblasts (NFs). Methylation profiles of 5 paired primary NSCLC fibroblast cell lines (CAFs) and normal lung fibroblasts (NFs) were generated. Genes were determined to be hyper- and hypo-methylated based on paired analysis.
2011-04-08 | E-GEOD-27284 | biostudies-arrayexpress