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Poster Display session 3

3373 - Development and characterization of salivary gland cancer organoid cultures

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Tumour Site

Head and Neck Cancers

Presenters

Wim Boxtel

Citation

Annals of Oncology (2019) 30 (suppl_5): v449-v474. 10.1093/annonc/mdz252

Authors

W.V. Boxtel1, T.M.W. Aalders2, G. Lassche1, I.C.H. van Engen - van Grunsven3, G.W. Verhaegh2, C. van Herpen1, J. Schalken2

Author affiliations

  • 1 Department Of Medical Oncology, Radboud University Medical Center, 6525 GA - Nijmegen/NL
  • 2 Department Of Urology, Radboud university medical center, 6525GA - Nijmegen/NL
  • 3 Department Of Pathology, Radboud University Medical Center, 6525 GA - Nijmegen/NL

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Abstract 3373

Background

Recently 3D organoid cell cultures have been established for a variety of human cancers. Salivary gland cancer (SGC) is a rare cancer with 22 different subtypes and few treatment options. Our aim is to generate a large repertoire of patient-derived SGC organoids with different phenotypes, which will facilitate pre-clinical and pharmacological studies.

Methods

Fresh tissues of resected primary tumours and/or metastases of SGC patients were collected. Tissues were minced and digested with collagenase type 2 and TrypLE to generate single cells. After washing, the cells were seeded in growth factor reduced Matrigel. Organoid medium, containing Rho kinase inhibitor Y27632, was refreshed twice a week. Viable organoids were characterized by immunohistochemistry and by DNA/RNA sequencing. Moreover, the organoids were used to evaluate various treatments that are or may be relevant for the treatment of SGC.

Results

Between 2016 and 2018 we obtained tissue of 17 SGC patients, of which 16 contained sufficient material for processing: 10 salivary duct carcinoma (SDC), 3 adenoid cystic carcinoma (ACC), 2 muco-epidermoid carcinoma (MEC) and 1 parotid adenocarcinoma not otherwise specified (NOS). For 5 tumors (2 SDC, 2 ACC, 1 adenocarcinoma NOS) viable organoids were established, which could be passaged at least three times. Organoids cultures derived from the other tumours stopped growing after the first passage. Viable organoids showed resemblance with the original primary tumour, based on morphology, protein expression, and growth pattern. Various drugs were tested at a single dose, and showed reduced organoid cell growth compared to untreated controls. Moreover, a dose-response relationship was established for an ALK-positive MEC organoid that was treated with crizotinib. Finally, epithelial-mesenchymal transition was shown in SDC organoids of a primary tumour and a lymph node metastasis of the same patient.

Conclusions

We are the first that have successfully developed and characterized long-term organoid cultures for ACC and SDC. These organoid cell lines will facilitate pre-clinical and pharmacological studies. Other SGC organoid cultures do not grow infinitely, but do provide an in vitro model to study different treatments during initial growth.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Radboud University Medical Center.

Funding

Dutch Salivary Gland Cancer Patient Platform.

Disclosure

All authors have declared no conflicts of interest.

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