Abstract
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.
Highlights
Head and neck squamous cell carcinomas (HNSCC) are the sixth most common cancer worldwide
We investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived Cancer-associated fibroblasts (CAFs) to promote or inhibit the colony-forming capability of HNSCC cells, and the effect of cisplatin on this promoting or inhibiting influence
To test a hypothesis that CAFs may affect the sensitivity of cancer cells to cisplatin, CAF-FaDu coculture was exposed to 5 μM cisplatin treatment
Summary
Head and neck squamous cell carcinomas (HNSCC) are the sixth most common cancer worldwide. The locoregional disease recurs in 60% of patients and metastatic disease arises in 15–25% [1]. For these reasons, chemotherapy (alone or in combination with radiotherapy) has an important role in the treatment of HNSCC. HNSCC represents a heterogeneous group of tumors with varying levels of cisplatin resistance. It was shown that stromal cells in tumor tissue may modulate the resistance to chemotherapy [4]. It was shown that drug resistance is likely to be reversible by removal of the tumor-supporting stromal cells [5]. We investigated the ability of HNSCC patient-derived CAFs to promote or inhibit the colony-forming capability of HNSCC cells, and the effect of cisplatin on this promoting or inhibiting influence. Subsequent analysis on FaDu and Detroit562 cell lines focused on changes in the expression of genes associated with: (1) pluripotency (NANOG, SOX2, POU5F, SNAIL); (2) cell division (FOLR1); (3) proliferative activity of tumor cells (MKI67); (4) angiogenesis (VEGFA); (5) acquisition of autonomous proliferative signalling (EGFR, EGF); (6) immune response (COX2, CCL2, IL6, EP3, PGE2S); and (7) cell cycle, and cell death modifications (BCL2, BIRC5, NFKB1, CAV1)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
