The effect of CPXM2-aligned collagen on gene expresssion and the intracellular signaling pathway in PaTu 8988t cells.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE292740 | GEO | 2025/12/04
REPOSITORIES: GEO
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Project description:The effect of CPXM2-aligned collagen on gene expresssion and the intracellular signaling pathway in PaTu 8988t cells.
| PRJNA1241172 | ENA
Project description:5×106 PaTu 8988t cells were spread into 10cm dish and then replaced into 5ml serum-free medium after being attached to the wall. At the same time, 5ml of the supernatant of PCAF-Ctrl, PCAF-CPXM2-WT and PCAF-CPXM2-mut stable cell strains were added to each group. After 8 hours, proteins from each group were collected for phosphorylated protein enrichment. The phosphorylated protein enrichment kit was used for this process, followed by protein mass spectrometry analysis of the signaling pathway of pancreatic cancer cells activated by collagen topology mediated by CPXM2.
2025-03-26 | PXD062248 |
Project description:Physiologic turnover of interstitial collagen is mediated by a sequential pathway, in which collagen is fragmented by pericellular collagenases, endocytosed by specific collagen receptors, and routed to lysosomes for degradation by lysosomal cathepsins. Here, we used intravital microscopy to investigate if malignant tumors, which are characterized by high rates of extracellular matrix turnover, utilize a similar collagen degradation pathway. Tumors of epithelial, mesenchymal, or neural crest origin all displayed vigorous endocytic collagen degradation with an abundance of cells engaged in this process. These cells were identified as tumor-associated macrophage (TAM)-like cells that degraded collagen in a mannose receptor-dependent manner. Accordingly, increased intra-tumoral collagen was observed in mannose receptor-deficient mice. Whole transcriptome profiling uncovered a distinct extracellular matrix-catabolic signature of these collagen-degrading TAMs. Lineage-ablation studies revealed that collagen-degrading TAMs originated from circulating CCR2+ monocytes. The study identifies a novel function of TAMs in altering the tumor microenvironment through endocytic collagen turnover and establishes macrophages as centrally engaged in tumor-associated collagen degradation.
2018-01-01 | GSE107053 | GEO
Project description:CD34+ hematopoietic stem/progenitor cells (HSC) reside in the bone marrow in close vicinity to the endosteal bone surface, surrounded by osteoblasts, stromal cells and various extracellular matrix molecules. We utilized a bioartificial matrix containing fibrillar collagen I, the major matrix component of bone, as scaffold for ex vivo expansion of HSCs. CD34+ HSCs were isolated from umbilical cord blood and cultivated within reconstituted collagen I fibrils in presence of FLT3-ligand, SCF and IL-3. After seven days of culture cell number, colony-forming units and gene expression profile of the cultured cells were assessed. Although the total expansion factor of CD34+ cells was slightly lower when cells were cultivated in the collagen I gel, the frequency of colony-forming units (CFU-C) increased compared to control suspension cultures. Gene expression analysis with microarray chip technology revealed the upregulation of more than 50 genes in presence of collagen I. Among them, genes for several growth factors, cytokines and chemokines (e.g. interleukin 8, MIP1-α) could be confirmed by quantitative PCR. Furthermore, increased expression of the negative cell-cycle regulator BTG2/TIS21 and an inhibitor of MAP kinase pathway, DUSP2, underline the regulatory role of the extracellular matrix. Together, these data show that the expansion of CD34+ cord blood cells in a culture system containing a three-dimensional collagen I matrix induces a qualitative change in the gene expression profile of cultivated HSCs. Keywords: hematopoietic stem/progenitor cells, collagen I, gene expression
2005-09-21 | GSE3003 | GEO
Project description:Pathological fibrosis, an excessive accumulation of collagen, compromises tissue architecture, impedes its function and represents a medical complication. Properties of the amniotic membrane have demonstrated potential to regulate fibrotic processes. RNA sequencing analysis evaluated the effects of dehydrated human amnion/chorion membrane (DHACM) on fibrotic events using in vitro macromolecular crowding to mimic a physiologically relevant microenvironment. Functional enrichment with Reactome pathway analysis indicated that the function of a subset of these dysregulated genes was associated with the composition and function of the extracellular matrix. Further use of macromolecular crowding in vitro was used to evaluate the effects of DHACM and a lyophilized human amnion/chorion membrane (LHACM) on type 1 collagen production and deposition under profibrotic conditions (addition of TGFβ1). In the continued presence of TGFβ1, LHACM and DHACM regulated the intracellular production and extracellular deposition of type 1 collagen. In addition, results suggest that the effect on collagen deposition could in part be modulated through the regulation of proteins responsible for the extracellular post-translational modifications of collagen. These observations may support the use of DHACM and LHACM in the regulation collagen production/deposition in profibrotic environments.
2024-05-06 | GSE247237 | GEO
Project description:The extracellular matrix has been shown to control breast epithelial cell morphogenesis, proliferation and signalling. Here we compared changes in gene expression between 4T1 murine mammary carcinoma cells grown in a low or high density collagen matrix
2019-02-16 | GSE78022 | GEO
Project description:We report RNA sequencing data from 2 cancer cell line (fibrosarcoma, HT1080 and Breast cancer, MDA-MB-231) and one non-canceours cell line (human foreskin fibroblast HFF) embbeded in two different 3D collagen matrix environements. The topographical organization of collagen within the tumor ECM has been implicated in guiding cancer cell migration and independently predicts progression to metastasis. Here, we show that collagen matrices with small pores and short fibers, but not Matrigel, trigger a conserved transcriptional response and subsequent motility switch in cancer cells that results in formation of multicellular network structures. The response is not mediated by hypoxia, matrix stiffness, or bulk matrix density, but by matrix architecture and beta1 integrin upregulation. The transcriptional module associated with network formation is enriched for migration and vasculogenesis-associated genes that predicted survival in patient data across nine distinct tumor types. Evidence at the protein level of this gene module is found in patient tumors displaying a vasculogenic mimicry (VM) phenotype. Our findings link a collagen matrix-induced migration program to VM, and suggest that this process may be broadly relevant to metastatic progression in solid human cancers.
2017-11-26 | GSE101209 | GEO
Project description:Lung cancer is the leading cause of cancer-related deaths in the world, and non-small cell lung cancer (NSCLC) is the most common subset. Although immune checkpoint inhibitors have improved outcomes in a subset of NSCLC patients, these effects are usually not durable. Thus, a more complete understanding of how immune niches within the tumor microenvironment (TME) promote NSCLC progression will allow us to build upon these advances. We previously found that infiltration of tumor inflammatory monocytes (TIMs) into lung squamous carcinoma (LUSC) tumors is associated with increased metastases and poor survival. To further understand how TIMs promote metastases, we compared RNA-seq profiles of TIMs from several LUSC metastatic models with IMs of non-tumor bearing controls. We identified Spon1, a secreted extracellular matrix glycoprotein, as upregulated in TIMs and that Spon1 expression in LUSC tumors corresponds with poor survival. Bioinformatic analyses of the Cancer Genome Atlas (TCGA) revealed that LUSC tumors with high SPON1 expression significantly enriched for collagen extracellular matrix (ECM) signatures. Unexpectedly, we observed SPON1+ TIMs mediate their effects directly through LRP8 (ApoER2) on NSCLC cells, which results in TGFβ1 activation and robust production of fibrillar collagens. Using several orthogonal approaches, we demonstrate that SPON1+ TIMs are sufficient to promote NSCLC metastases. Additionally, we find that Spon1 loss in the host, or Lrp8 loss in cancer cells, results in a significant decrease of both high-density collagen matrices and metastases. Finally, we confirm the relevance of the SPON1/LRP8/TGFβ1 axis with collagen production and survival in NSCLC patients. Taken together, our study describes how SPON1+ TIMs promotes collagen remodeling and NSCLC metastases through an LRP8-TGFβ1 signaling axis in lung cancer cells.
2024-03-05 | GSE260524 | GEO
Project description:Despite the growing recognition of the role of the stroma in cancer growth, invasive behavior and metastasis, the exact mechanisms of its participation remain unclear. We have explored the relationships between the epithelial/mesenchymal (E/M) state of colorectal cancer cells, their ability to activate fibroblasts, and the expression of collagen related genes. To this end, we studied (i) co-cultures of colorectal cancer cells with different hybrid E/M states and normal fibroblasts in a collagen matrix and (ii) patient-derived cancer-associated fibroblasts (CAFs). Using RNA-sequencing, we found that the different cancer cells can activate normal fibroblasts, which could form dense collagen networks. The functional enrichment analysis of differentially expressed genes indicates more mesenchymal phenotype and greater motility of SW480 cells compared to HT29 cells. The genes related to collagen biosynthesis and catabolism tend to be more active in SW480 cells rather than HT29 cells. Moreover, LOXL2 and LOXL3 genes, which are necessary for collagen fibril organization, are SW480 specific, which may indicate greater input of this cell line in collagen remodeling compared to HT29 cells. The expression of several CAF marker genes is activated in NFs upon co-cultivation with HT29 and SW480. Interestingly, a more-epithelial cell line HT29 activates the fibroblasts to a greater extent, than does SW480. The co-cultivation of colon cancer cell lines HT29 or SW480 with NFs leads to the activation of collagen biosynthesis and collagen fibril organization genes in NFs. Our findings suggest that the normal fibroblasts, activated by cancer cells, contribute to the organization of the extracellular matrix. Therefore, targeting the ability of cancer cells to activate normal fibroblasts can be considered as a new therapeutic strategy.
2020-10-30 | GSE155343 | GEO
Project description:Communications between cardiomyocytes and fibroblasts in the heart are thought to occur through both secreted growth factors and via alterations in the structural properties of the extracellular matrix that each of the cell types helps generate. While perturbations in fibroblast activity are known to impact development of cardiomyocyte hypertrophy, the specific role played by collagen in this intercellular communication remains unknown. In this study we addressed this knowledge gap through differential regulation of collagen 1a2 using mouse hearts. The microarray assays reported here were carried out to assess the effects of collagen 1a2 ablation on cardiac transcriptional profiles.
2023-09-15 | GSE204724 | GEO