Background: Patient-derived tumour xenografts (PDTX) are powerful tools that have helped accelerate the rate of new discoveries especially with respect to targeted therapies. Although they more closely recapitulate tumour heterogeneity and tissue architecture compared to cell line xenografts, few studies have adopted this technique for oesophageal adenocarcinoma. This may be due to a lower rate of engraftment, compared to other tumours, when using the standard subcutaneous transplantation technique. We postulated that an intramuscular technique may improve engraftment owing to a greater blood supply within the transplant bed. Therefore, the aim of this study was to compare engraftment rates using an intramuscular versus subcutaneous transplantation technique.
Method: Specimens of oesophageal adenocarcinoma, both pre and post chemoradiotherapy, were obtained from surgical resections and endoscopic biopsies. They were divided into 1mm pieces and soaked in Matrigel prior to transplantation into an immunocompromised (SCID or NOD SCID) mouse (F0), either subcutaneously into the flank or intramuscularly into the dorsum. Mice were monitored for tumour formation and culled once a tumour reached a volume of 1500 mm3 or the mouse displayed signs of suffering. Tumours were then serially passaged into a second mouse (F1), cryopreserved for later passaging, and compared to the original tumours using histological and immunohistochemical analysis.
Results: Engraftment of F0 PDTX took an average of three months. However, engraftment of passaged F1 xenografts were first evident after just five weeks. Four of the five established tumours were derived using the intramuscular technique. F0 PDTX showed similar architectural features and antibody staining (anti-human mitochondrial & SOX9) compared to the original tumour. Tumour behaviour also matched that seen in the patient and pulmonary micrometastases were also evident in one specimen.
Summary: Preliminary results reveal a trend towards a higher engraftment rate using an intramuscular transplantation technique and also demonstrate the feasibility of using PDTX to study oesophageal adenocarcinoma.