Published online Feb 21, 2018. doi: 10.3748/wjg.v24.i7.794
Peer-review started: December 2, 2017
First decision: December 20, 2017
Revised: January 14, 2018
Accepted: January 18, 2018
Article in press: January 18, 2018
Published online: February 21, 2018
To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice.
This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations (intraperitoneal, subcutaneous and pancreatic). Histological analysis (haematoxylin-eosin and Masson’s trichrome staining) and immunohistochemical assessment of apoptosis (TUNEL), proliferation (Ki-67), angiogenesis (CD31) and fibrogenesis (α-SMA) were performed. When a tumour xenograft reached the target size, it was re-implanted in a new nude mouse. Three sequential tumour xenograft generations were generated (F1, F2 and F3).
The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth (69.9%), followed by intraperitoneal (57.6%) and pancreatic (55%) models. Tumour development was faster in the subcutaneous model (17.7 ± 2.6 wk) compared with the pancreatic (23.1 ± 2.3 wk) and intraperitoneal (25.0 ± 2.7 wk) models (P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models (F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics.
In our experience, the faster development and greatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer.
Core tip: Several investigations have established patient-derived xenograft models for breast, renal, head and neck cancer, and hepatocellular tumours. Some of these models have predicted the clinical response of a specific type of tumour to different chemotherapeutic agents. However, the morphological and histological features of human pancreatic cancer xenografts in experimental models have been poorly studied. In the present study, the effectiveness of three experimental models based on the implantation of patient pancreatic cancer in three different locations (subcutaneous, intraperitoneal and pancreatic) have been assessed for the first time.