Cultivation of Head and Neck Squamous Cell Carcinoma Cells with Wound Fluid Leads to Cisplatin Resistance via Epithelial-Mesenchymal Transition Induction.
Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance.
['Meyer|Till Jasper|TJ|0000-0003-2377-3519', 'Stöth|Manuel|M|', 'Moratin|Helena|H|', 'Ickrath|Pascal|P|0000-0001-8775-1330', 'Herrmann|Marietta|M|0000-0002-2412-7474', 'Kleinsasser|Norbert|N|', 'Hagen|Rudolf|R|0000-0003-4735-700X', 'Hackenberg|Stephan|S|0000-0001-6995-1849', 'Scherzad|Agmal|A|']
D000368:Aged D000369:Aged, 80 and over D001826:Body Fluids D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D002945:Cisplatin D016207:Cytokines D019008:Drug Resistance, Neoplasm D058750:Epithelial-Mesenchymal Transition D005260:Female D006258:Head and Neck Neoplasms D006801:Humans D008297:Male D008875:Middle Aged D000077195:Squamous Cell Carcinoma of Head and Neck D014947:Wounds and Injuries
head and neck squamous cell carcinoma wound fluid cisplatin resistance epithelial-mesenchymal transition Interleukin cell proliferation