Sponge-supported cultures of primary head and neck tumors for an optimized preclinical model

A.J.C. Dohmen, J. Sanders, S. Canisius, E.S. Jordanova, E.A. Aalbersberg, M.W.M. van den Brekel, J. Neefjes, C.L. Zuur

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Treatment of advanced head and neck cancer is associated with low survival, high toxicity and a widely divergent individual response. The sponge-gel-supported histoculture model was previously developed to serve as a preclinical model for predicting individual treatment responses. We aimed to optimize the sponge-gel-supported histoculture model and provide more insight in cell specific behaviour by evaluating the tumor and its microenvironment using immunohistochemistry. We collected fresh tumor biopsies from 72 untreated patients and cultured them for 7 days. Biopsies from 57 patients (79%) were successfully cultured and 1451 tumor fragments (95.4%) were evaluated. Fragments were scored for percentage of tumor, tumor viability and proliferation, EGF-receptor expression and presence of T-cells and macrophages. Median tumor percentage increased from 53% at day 0 to 80% at day 7. Viability and proliferation decreased after 7 days, from 90% to 30% and from 30% to 10%, respectively. Addition of EGF, folic acid and hydrocortisone can lead to improved viability and proliferation, however this was not systematically observed. No patient subgroup could be identified with higher culture success rates. Immune cells were still present at day 7, illustrating that the tumor microenvironment is sustained. EGF supplementation did not increase viability and proliferation in patients overexpressing EGF-Receptor.
Original languageEnglish
Pages (from-to)25034-25047
JournalOncotarget
Volume9
Issue number38
DOIs
Publication statusPublished - May 2018

Funding

This work was supported by the Riki Foundation awarded to CZ and MB, and by a NWO TOP grant awarded to JN and HO.

FundersFunder number
Riki Foundation
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

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