ArticlePloS one2015
Cancer-associated fibroblasts in a human HEp-2 established laryngeal xenografted tumor are not derived from cancer cells through epithelial-mesenchymal transition, phenotypically activated but karyotypically normal.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Characterizing a murine breast cancer mouse model reveals chromosomal abnormalities in structure and number of single-cell clones and the presence of rare cancer stem cell-like phenotypes.Animal models and experimental medicine · 2026Article
- Exploring the diversity of cancer-associated fibroblasts: insights into mechanisms of drug resistance.Frontiers in cell and developmental biology · 2024Review
- Heterogeneity of cancer-associated fibroblasts in head and neck squamous cell carcinoma: opportunities and challenges.Cell death discovery · 2023Review
- Head and Neck Squamous Cell Carcinoma: Risk Factors, Molecular Alterations, Immunology and Peptide Vaccines.International journal of peptide research and therapeutics · 2022Review
- Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients.Journal of clinical laboratory analysis · 2022Article
- Tumor-Derived Extracellular Vesicles Activate Normal Human Fibroblasts to a Cancer-Associated Fibroblast-Like Phenotype, Sustaining a Pro-Tumorigenic Microenvironment.Frontiers in oncology · 2022Article
- Deeper insights into transcriptional features of cancer-associated fibroblasts: An integrated meta-analysis of single-cell and bulk RNA-sequencing data.Frontiers in cell and developmental biology · 2022Article
- TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer.International journal of molecular sciences · 2018Review
- Podoplanin is an important stromal prognostic marker in perihilar cholangiocarcinoma.Oncology letters · 2018Article
- Fibroblasts, an inconspicuous but essential player in colon cancer development and progression.World journal of gastroenterology · 2016Review
- Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression and even initiation. However, the origins of CAFs in various cancer types remain controversial, and one of the important hypothesized origins is through epithelial-mesenchymal transition (EMT) from cancer cells. In this study, we investigated whether the HEp-2 laryngeal cancer cells are able to generate CAFs via EMT during tumor formation, which is now still unknown. The laryngeal xenografted tumor model was established by inoculating the HEp-2 laryngeal cancer cell line in nude mice. Primary cultured CAFs from the tumor nodules and matched normal fibroblasts (NFs) from the adjacent connective tissues were subcultured, purified, and verified by immunofluorescence. Migration, invasion, and proliferation potentials were compared between the CAFs and NFs. A co-culture of CAFs with HEp-2 cells and a co-injection of CAFs with HEp-2 cells in nude mice were performed to examine the cancer-promoting potential of CAFs to further verify their identity. Karyotypic analyses of the CAFs, NFs, and HEp-2 cells were conducted. A co-culture of NFs with HEp-2 cells was also performed to examine the expression of activated markers of CAFs. A pathological examination confirmed that the laryngeal xenografted tumor model was successfully established, containing abundant CAFs. Immunocytochemical staining verified the purities and identities of the CAFs and NFs. Although the CAFs manifested higher migration, invasion, proliferation, and cancer-promoting capacities compared with the NFs, an analysis of chromosomes revealed that both the CAFs and NFs showed typical normal mouse karyotypes. In addition, the NFs co-cultured with HEp-2 cells did not show induced expressions of activated markers of CAFs. Our findings reveal that the CAFs in the HEp-2 established laryngeal xenografted tumor are not of laryngeal cancer origin but of mouse origin, indicating that the HEp-2 laryngeal cancer cells cannot generate their own CAFs via EMT in this model.
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