Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts

Peltanova, Barbora; Liskova, Marketa; Gumulec, Jaromir; Raudenska, Martina; Polanska, Hana Holcova; Vaculovic, Tomas; Kalfert, David; Grega, Marek; Plzak, Jan; Betka, Jan; Masarik, Michal

doi:10.3390/ijms22041912

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Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts

¹,

^1,2,3,

Hana Holcova Polanska

^1,2,

⁴,

⁵

⁶,

⁵

⁵ and

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Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic

Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-625 00 Brno, Czech Republic

Department of Chemistry and Biochemistry, Mendel University, Zemedelska 1, CZ-613 00 Brno, Czech Republic

⁴

Department of Chemistry, Faculty of Science, Masaryk University, Kotlarska 2, CZ-611 37 Brno, Czech Republic

⁵

Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Motol, First Faculty of Medicine, Charles University, V Uvalu 84, 150 06 Prague 5, Czech Republic

⁶

Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Uvalu 84, 150 06 Prague 5, Czech Republic

⁷

BIOCEV, First Faculty of Medicine, Charles University, Prumyslova 595, CZ-252 50 Vestec, Czech Republic

Author to whom correspondence should be addressed.

Academic Editor: A. Phillip West

Int. J. Mol. Sci. 2021, 22(4), 1912; https://doi.org/10.3390/ijms22041912

Received: 6 January 2021 / Revised: 29 January 2021 / Accepted: 6 February 2021 / Published: 15 February 2021

(This article belongs to the Special Issue Advances in Cancer Metabolism and Tumour Microenvironment)

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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. View Full-Text

Keywords: head and neck cancer; cancer-associated fibroblasts; cisplatin; treatment resistance; cancer recurrence; patient-derived cell cultures; coculture

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Peltanova, B.; Liskova, M.; Gumulec, J.; Raudenska, M.; Polanska, H.H.; Vaculovic, T.; Kalfert, D.; Grega, M.; Plzak, J.; Betka, J.; Masarik, M. Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts. Int. J. Mol. Sci. 2021, 22, 1912. https://doi.org/10.3390/ijms22041912

AMA Style

Peltanova B, Liskova M, Gumulec J, Raudenska M, Polanska HH, Vaculovic T, Kalfert D, Grega M, Plzak J, Betka J, Masarik M. Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts. International Journal of Molecular Sciences. 2021; 22(4):1912. https://doi.org/10.3390/ijms22041912

Chicago/Turabian Style

Peltanova, Barbora, Marketa Liskova, Jaromir Gumulec, Martina Raudenska, Hana H. Polanska, Tomas Vaculovic, David Kalfert, Marek Grega, Jan Plzak, Jan Betka, and Michal Masarik. 2021. "Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts" International Journal of Molecular Sciences 22, no. 4: 1912. https://doi.org/10.3390/ijms22041912

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Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts

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