Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different "sensitizing ratio". Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.
- MeSH
- chemorezistence účinky léků MeSH
- cisplatina farmakologie MeSH
- dlaždicobuněčné karcinomy hlavy a krku metabolismus patologie MeSH
- fibroblasty asociované s nádorem účinky léků metabolismus MeSH
- kokultivační techniky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru metabolismus patologie MeSH
- nádorové buněčné linie MeSH
- nádory hlavy a krku metabolismus patologie MeSH
- parakrinní signalizace účinky léků MeSH
- protinádorové látky farmakologie MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- testy nádorových kmenových buněk MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
