Impact of Thapsigargin and Trifluoperazine on tumor growth and lymphogenic metastasis of head and neck carcinomas in an orthotopic murine in vivo model

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Introduction Cervical lymph node metastases are detected in approximately 50% of all HNSCC patients at initial tumor diagnosis associated with a worse prognosis. Using a newly established orthotopic murine in vivo model, we are able to test two potential anti-metastatic and – proliferative agents that place the cell in a significant Ca2+ stress state and thus prevent tumor cells from metastasizing. Material and Methods Cells from a HNSCC cell line (FaDu) were inoculated into the tip of the tongue of 40 immunodeficient mice (NOD.CB17/Prkdc scid/scid /Rj). Within the next 5-7 weeks, metastastatic spread into cervical lymph nodes takes place. Animals were treated with thapsigargin and/or trifluoperazine during oberservation period. The primary tumors and cervical lymph node metastases were histologically processed and analyzed. Results By the administration of trifluoperazine and/or thapsigargin we were able to achieve an overall reduction of metastasis of about 12% within 40 animals that were inoculated with tumor cells. In case of only trifluoperazine administration we could achieve a reduction of 16% in metastasis formation (p=0.214). There is a significant difference in size of detected metastases. Only macro-metastases (>20 tumor cells) were detected in control animals. Significantly more micro-metastases (<20 cells) were found when thapsigargin was administered (p=0.031). Discussion The results of this in vivo study indicate that the two potential therapeutics show an effect on metastasis in general, as well as on the size of metastases. The limited number of animals impairs a significant result but shows an interesting trend. Obtained results give reasons to extend this study to explore detailed insights into the mechanisms of action. Else-Kröner-Fresenius Stiftung Publication History Article published online: 24 May 2022 © 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/). Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

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