Objectives: We have previously demonstrated activity of Apo2L/TRAIL against patient pancreatic tumor xenografts. Here, we have examined the influence of the tumor implantation site on therapeutic response of orthotopic tumors and their metastases to Apo2L/TRAIL.
Methods: Sensitivity of 6 patient pancreatic tumor xenografts to Apo2L/TRAIL was determined in a subcutaneous model. To compare the response of orthotopic tumors, cells from subcutaneous xenografts were injected into the pancreas. Tumor growth was confirmed by histological examination of selected mice, and then treatment was started. When all control mice developed externally palpable tumors, the experiment was terminated, and pancreatic weights compared between control and treated groups. Magnetic resonance imaging was used to quantitate the response of orthotopic and metastatic tumors.
Results: The sensitivity to Apo2L/TRAIL observed in subcutaneous tumors was maintained in orthotopic tumors. Metastatic spread was observed with orthotopic tumor implantation. In an orthotopic model of a sensitive tumor, primary and metastatic tumor burden was significantly reduced, and median survival significantly extended by Apo2L/TRAIL therapy.
Conclusions: Our data provide evidence that the site of tumor engraftment does not alter the inherent sensitivity of patient xenografts to Apo2L/TRAIL, and these results highlight the potential of Apo2L/TRAIL therapy against primary and metastatic pancreatic cancer.