Differential effect of cancer-associated fibroblasts on HNSCC progression: Cancer Promotion or inhibition
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PROVIDER: PRJNA674840 | ENA |
REPOSITORIES: ENA
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Project description:To study of differential effect on cancer-associated fibroblasts of HNSCC, we have employed microarray expression profiling. The critical effect of the tumor microenvironment to caner progression is well recognized. Recent research suggests that the cancer-promoting properties of the tumor stroma may attributed to fibroblasts. However, little is known about fibroblasts that inhibit cancer progression. From the immunohistochemical analysis of cancer tissues from head and neck squamous cell carcinoma (HNSCC) patients, we divided cancer-associated fibroblast (CAF) into two groups depending on whether the boundary between epithelial cancer cells and the surrounding extracellular matrix (ECM) is clear and smooth or not. Therefore, we tried to evaluate whether there is a difference between these two CAFs in HNSCC progression. CAF was primary cultured, followed by co-culture with HNSCC cell to observe the effect on Matrigel invasion. The mRNA expression patterns between these two CAF groups were compared by DNA microarray analysis. FaDu cell and primary CAF from each group was co-transplanted into the oral mucosa of mice, and the tumorigenesis was compared. The CAF group (CAF-Promote, CAF-P) from cancer tissues which have unclear boundary between ECM and epithelial cancer cells showed a tendency to stimulate in vitro Matrigel invasion of HNSCC cell. On the contrary, the CAF group (CAF-Defense, CAF-D) from cancer tissues, which have clear boundary with epithelial cancer cell caused no remarkable increase of Matrigel invasion. In addition, CAF-D reduced the tumorigenicity of FaDu compared to CAF-P in the in vivo mice model. In DNA microarray analysis, COL3A1, COL6A6, COL25A1, and COL26A1 were particularly highly expressed in CAF-D group. In this study, these collagen proteins derived from cancer stroma were found to have a function of inhibiting the progression of HNSCC. It is expected to provide important information for predicting the prognosis of HNSCC and development of drug target in the future.
2021-02-18 | GSE160919 | GEO
Project description:The cancer cells selectively promote the translation of specific oncogenic transcripts to stimulate cancer progression. Although growing evidence has revealed that tRNA modifications and related genes participate in this process, their roles in head and neck squamous cell carcinoma (HNSCC) remain largely uncharacterized. Here we found that tRNA m7G methyltransferase complex components METTL1/WDR4 were both upregulated in HNSCC and associated with poor prognosis. Functionally, METTL1/WDR4 promoted HNSCC progression and metastasis in cell-based and transgenic mouse models. Mechanistically, ablation of METTL1 reduced m7G levels of 16 tRNAs, causing translational inhibition of a subset of oncogenic transcripts, including the genes related to PI3K/AKT/mTOR signaling pathway. In addition, chemical modulators of PI3K/AKT/mTOR signaling pathway can reverse the effects of Mettl1 in HNSCC. Furthermore, single-cell RNA sequencing results revealed that depletion of Mettl1 in tumor cells altered the immune landscape and cell-cell interaction between tumor and stromal compartment. In summary, this study uncovered the physiological function and mechanism of mis-translation regulation mediated by tRNA m7G modification in HNSCC, and suggested that targeting METTL1 could be a promising treatment strategy for HNSCC patients.
2022-03-23 | GSE172146 | GEO
Project description:Background: The critical effect of the tumor microenvironment on cancer progression is well recognized. Recent research suggests that the cancer-promoting properties of the tumor stroma may be attributed to fibroblasts. However, the effect of cancer-associated fibroblast (CAF) on the progression of head and neck squamous cell carcinoma (HNSCC) is not well known. Methods: From the immunohistochemical analysis of head and neck squamous cell carcinoma (HNSCC) tissues, we divided CAF into two groups depending on the presence or absence of a well-demarcated boundary between epithelial cancer cells and the surrounding extracellular matrix (ECM). Primary culture of CAF was performed, followed by co-transplantation with HNSCC cells into mice oral mucosa, and the tumorigenesis was compared. The mRNA expression patterns between these two CAF groups were compared using DNA microarray analysis. Results: CAFs from cancer tissues that showed no demarcation between ECM and epithelial cancer cells (CAF-Promote) tended to stimulate Matrigel invasion of HNSCC cells. Conversely, CAFs from cancer tissues that showed a boundary with epithelial cancer cells (CAF-Delay) caused no remarkable increase in Matrigel invasion. Compared with CAF-P, CAF-D is less effective in promoting FaDu tumorigenicity in the mouse model. In DNA microarray analysis, COL3A1 and COL6A6 showed particularly high expression in the CAF-D group. Conclusions: These cancer stroma-derived collagen proteins might delay the HNSCC progression. These findings are expected to provide vital information for predicting HNSCC prognosis and developing drug targets in the future.
| S-EPMC7915931 | biostudies-literature
Project description:Head and neck squamous cell carcinoma (HNSCC) undergoes stepwise progression from normal tissue to metastasized tumors. To comprehensively delineate the heterogeneity of tumor cells and their interactions during the progression of HNSCC, we employed single-cell RNA-seq (scRNA-seq) profiling for the tissues of normal, leukoplakia, HNSCC, and metastasized HNSCC. We identified novel clones of malignant cells expressing LGALS7B and fibroblasts expressing CXCL8, and the abundance of these cells in the tumor tissue was associated with poorer prognostic outcomes. In addition, we demonstrated that fibroblasts in leukoplakia and tumor tissue express COL1A1, which interacts with CD44+ malignant cells, facilitating HNSCC progression. CD4+FOXP3+ regulatory T cells expand in leukoplakia and express LAIR2 with collagen stimulation, which may provide a favorable microenvironment for tumor progression. In conclusion, stromal and immune cell interactions play critical roles in the stepwise progression of HNSCC, and we have identified steps during HNSCC progression for possible therapeutic interventions
2022-08-31 | GSE181919 | GEO
Project description:Exosomes were isolated from plasma of n = 12 healthy donors (HD) and n = 16 head and neck cancer (HNSCC) patients. miRNA profiling of exosomes was performed using nCounter SPRINT system. miRNAs being predicted to target EMT-related genes (CDH1, VIM, TWIST1 and SNAI1/2) were selected and compared between HD and HNSCC patients.
2022-11-09 | E-MTAB-12408 | biostudies-arrayexpress
Project description:Cancer associated fibroblasts play an important role in prostate cancer progression
| PRJNA882042 | ENA
Project description:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer and is major cause of cancer mortality and morbidity. It emerges within oral cavity, lip, tongue, floor of the mouth, nasopharynx, palate, gingival and larynx, is common cancer worldwide especially in Southeast Asia and Southern China. Despite of the advancements in the understanding of the HNSCC as the disease, the 5 year survival rate remains unchanged at 50% since last three decades. Factors such as advanced stage presentation of the patient and consequent delay in diagnosis contributes to the bleak scenario. Thus, therefore there is dire need of useful biomarkers that can predict HNSCC in early stages and can serve as prognostic indicators or targets for treatment. In the present study, We used iTRAQ (isobaric tags for relative and absolute quantitation)-based quantitative proteomic approach followed by liquid chromatography and high resolution tandem mass spectrometry (LC-MS/MS) to identify differential proteins from head and neck cancer cell lines.
2015-01-29 | PXD000737 | Pride
Project description:To understand the cell types changes in prostate cancer progression, we carried out scRNA-seq of prostates from different kinds of genetic mouse model. After that, we found fibroblasts were changed obviously during prostate cancer progression. To confirm the function of the fibroblasts, LNCap was used to cocultured with all kinds of fibroblasts in control or ADT condition. To find out the key enviroment factors induced firoblast changing, RNA-seq, ATAC-seq and ChIP-seq of fibroblast in different treatment were taken. And finally, ADT, TGF-β1, and sox4 were confirmed as contributors of the stroma cell changes, which provided new strategies for prostate cancer treatment. scRNA-seq were used to find out the cell lines diverisity of prostate cancer progressiom. RNA-seq of LNCap cocultured with different fibroblasts were taken to identify the pathway fibroblasts induced. RNA-seq, ATAC-seq and ChIP-seq of fibroblasts were carried out to find out the reason of fibroblast changes.
2023-06-22 | GSE213665 | GEO
Project description:To understand the cell types changes in prostate cancer progression, we carried out scRNA-seq of prostates from different kinds of genetic mouse model. After that, we found fibroblasts were changed obviously during prostate cancer progression. To confirm the function of the fibroblasts, LNCap was used to cocultured with all kinds of fibroblasts in control or ADT condition. To find out the key enviroment factors induced firoblast changing, RNA-seq, ATAC-seq and ChIP-seq of fibroblast in different treatment were taken. And finally, ADT, TGF-β1, and sox4 were confirmed as contributors of the stroma cell changes, which provided new strategies for prostate cancer treatment. scRNA-seq were used to find out the cell lines diverisity of prostate cancer progressiom. RNA-seq of LNCap cocultured with different fibroblasts were taken to identify the pathway fibroblasts induced. RNA-seq, ATAC-seq and ChIP-seq of fibroblasts were carried out to find out the reason of fibroblast changes.
2023-06-22 | GSE213664 | GEO
Project description:To understand the cell types changes in prostate cancer progression, we carried out scRNA-seq of prostates from different kinds of genetic mouse model. After that, we found fibroblasts were changed obviously during prostate cancer progression. To confirm the function of the fibroblasts, LNCap was used to cocultured with all kinds of fibroblasts in control or ADT condition. To find out the key enviroment factors induced firoblast changing, RNA-seq, ATAC-seq and ChIP-seq of fibroblast in different treatment were taken. And finally, ADT, TGF-β1, and sox4 were confirmed as contributors of the stroma cell changes, which provided new strategies for prostate cancer treatment. scRNA-seq were used to find out the cell lines diverisity of prostate cancer progressiom. RNA-seq of LNCap cocultured with different fibroblasts were taken to identify the pathway fibroblasts induced. RNA-seq, ATAC-seq and ChIP-seq of fibroblasts were carried out to find out the reason of fibroblast changes.
2023-06-22 | GSE213663 | GEO