ArticleJournal of cancer research and clinical oncology2013
Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer.
Article in Journal of cancer research and clinical oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 34 citations in OpenAlex.
- Cancer‑associated fibroblasts in human malignancies, with a particular emphasis on sarcomas (Review).International journal of oncology · 2025Review
- Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-β/Smad pathway.Acta biochimica et biophysica Sinica · 2022Article
- Possible disease-protective roles of fibroblasts in cancer and fibrosis and their therapeutic application.Nagoya journal of medical science · 2022Review
- A narrative review on tumor microenvironment in oligometastatic and oligoprogressive non-small cell lung cancer: a lot remains to be done.Translational lung cancer research · 2021Review
- Mitochondria at Center of Exchanges between Cancer Cells and Cancer-Associated Fibroblasts during Tumor Progression.Cancers · 2020Review
- Tumor protein p53-induced nuclear protein 2 modulates osteogenic differentiation of human adipose derived stem/stromal cells by activating Wnt/β-catenin signaling.American journal of translational research · 2020Article
- ALI multilayered co-cultures mimic biochemical mechanisms of the cancer cell-fibroblast cross-talk involved in NSCLC MultiDrug Resistance.BMC cancer · 2019Article
- Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin β1 and PI3K.Scientific reports · 2015Article
- Article
- Crosstalk with cancer-associated fibroblasts induces resistance of non-small cell lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibition.OncoTargets and therapy · 2015Article
- Hierarchical paracrine interaction of breast cancer associated fibroblasts with cancer cells via hMAPK-microRNAs to drive ER-negative breast cancer phenotype.Cancer biology & therapy · 2015Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCancer-associated fibroblasts (CAFs) contribute to tumor progression through multiple pathways. However, the effect of CAFs on gene expression in lung cancer has been largely unknown. Here we systematically compared the gene expression changes in lung cancer cells induced by normal fibroblasts and CAFs.
methodsWound healing and cell proliferation assays were used to identify the property of CAFs used in this study. We used cDNA microarray analysis to compare gene expression in lung cancer cells cultured with either conditioned medium (CM) from lung CAFs or normal lung fibroblasts, the result of which was confirmed by RT-PCR and Western blot analysis. Immunohistochemistry on tissue sections from lung cancers was conducted to further confirm the results of cDNA microarray analysis.
resultsThe expression of many genes was upregulated in cancer cells by CAF CM, particularly cell adhesion molecules, integrins, and anti-apoptotic protein Bcl-2. Expression of integrins appeared to be upstream from Bcl-2. We identified transforming growth factor-β as a candidate factor that induced the expression of those genes in cancer cells. Immunohistochemical studies of clinical lung cancer tissues revealed that integrins and Bcl-2 were more highly expressed in the leading cells (LCs) than in the following cells, at the invasive front of cancer nests, which are adjacent to or in proximity to the stroma. Furthermore, the expression of integrins and Bcl-2 in LCs had a tendency to correlate with the clinical stage of cancer progression, including lymph node metastasis.
conclusionsOur results suggest that CAFs promote lung cancer progression partly through the direct regulation of gene expression in the LCs of invasive cancer nests.
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