Oncotarget

Research Papers:

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

Amy J.C. Dohmen, Joyce Sanders, Sander Canisius, Ekaterina S. Jordanova, Else A. Aalbersberg, Michiel W.M. van den Brekel, Jacques Neefjes and Charlotte L. Zuur _

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Oncotarget. 2018; 9:25034-25047. https://doi.org/10.18632/oncotarget.25244

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Abstract

Amy J.C. Dohmen1, Joyce Sanders2, Sander Canisius3, Ekaterina S. Jordanova4, Else A. Aalbersberg1,7, Michiel W.M. van den Brekel1,5, Jacques Neefjes6,8 and Charlotte L. Zuur1,5

1Department of Head and Neck Oncology and Surgery, Antoni van Leeuwenhoek, Amsterdam, The Netherlands

2Department of Pathology, the Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands

3Department of Computational Cancer Biology, the Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands

4Center for Gynecological Oncology Amsterdam, VUmc, Amsterdam, The Netherlands

5Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

6Division of Cell Biology, the Netherlands Cancer Institute, Amsterdam, The Netherlands

7Department of Nuclear Medicine, the Netherlands Cancer Institute, Amsterdam, The Netherlands

8Department of Chemical Immunology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence to:

Charlotte L. Zuur, email: c.zuur@nki.nl

Keywords: head and neck cancer; squamous cell carcinoma; primary tissue; cell culture; sponge gel supported histoculture

Received: September 13, 2017     Accepted: April 07, 2018     Published: May 18, 2018

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.


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