An orthotopic model of ductal adenocarcinoma of the pancreas in severe combined immunodeficient mice representing all steps of the metastatic cascade.
BACKGROUND
Clinically relevant animal models are needed to evaluate new therapeutic strategies against pancreatic adenocarcinoma, which is almost incurable by established treatment.


OBJECTIVE
To establish and characterize a metastatic orthotopic transplant model for pancreatic ductal adenocarcinoma in severe combined immunodeficient (SCID) mice.


METHODS
Human pancreatic ductal carcinoma cells, PancTu 1, were implanted either subcutaneously or orthotopically into the pancreas.


RESULTS
After 4 weeks, orthotopic transplantation resulted in an extensive local tumor growth of an undifferentiated ductal adenocarcinoma with slight to moderate desmoplastic reaction. The tumor growth and spread resembled the situation in humans, including invasion into adjacent organs causing biliary and stomach obstruction. In addition, tumor metastases to regional lymph nodes of the pancreas, lung, liver, mesentery, and diaphragm, and attached to the kidneys, spleen, and reproductive organs were observed. In contrast, no invasion or metastases could be demonstrated by subcutaneous implanted PancTu I cells. Using immunohistochemical analysis, even single human tumor cells could be detected in blood vessels and metastatic organs, providing evidence that the orthotopic transplant model appropriately reflects the entire process of the metastatic cascade.


CONCLUSIONS
This cancer model in SCID mice appears to be a powerful tool to investigate the identity of metastasis-associated genes and to evaluate preclinically the potency of novel antimetastatic agents in ductal adenocarcinoma of the pancreas.
Alves
F
F
Department of Hematology and Oncology, Georg-August-University, Göttingen, Germany. falves@gwdg.de
Contag
S
S
Missbach
M
M
Kaspareit
J
J
Nebendahl
K
K
Borchers
U
U
Heidrich
B
B
Streich
R
R
Hiddemann
W
W
D000818:Animals; D018395:CA-19-9 Antigen / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000473:pathology*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology*; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D018395:CA-19-9 Antigen; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D019394:Ki-67 Antigen; D015534:Trans-Activators; D051176:beta Catenin; D020778:Matrix Metalloproteinase 2