Bone marrow-derived progenitor cells could modulate pancreatic cancer tumorigenesis via peritumoral microenvironment in a rat model.
Metaplastic tubular complexes (MTC) have been proposed as precursor lesions for pancreatic adenocarcinoma (PDAC). In this study, we investigated the potential role of bone marrow-derived progenitor cells (BMPC) in the formation of MTC and PDAC in a rat model. F344 rats defective for CD26 (dipeptidyl peptidase IV, DPPIV) expression were sublethally irradiated and received rescue bone marrow cells from wild-type F344 rats that express CD26. After confirming engraftment, recipient animals received dimethylbenzanthracene (DMBA) implantation in their pancreas. Animals were sacrificed monthly from 3 to 7 months. We observed both MTC and tumors in animals that received DMBA. These MTC were ductal complexes because they stained positive for cytokeratin but were negative for chymotrypsin and chromogranin A. Cells that expressed both CD26 and cytokeratin were rarely observed in the MTC. Cells expressing either both CD26 and CD45 or CD26 and smooth muscle actin were also found near the MTC. However, no CD26 signal was detected in the tumors. Within this model, there appeared to be no evidence supporting that BMPC turned into tumor cells directly. BMPC could modulate pancreatic cancer growth through tumor microenvironment.
Pan
Jen-Jung
JJ
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA. jenjung.pan@medicine.ufl.edu
Oh
Seh-Hoon
SH
Lee
Wayne C
WC
Petersen
Bryon E
BE
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D002273:Carcinogens / Q000633:toxicity; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D017493:Leukocyte Common Antigens; D018819:Dipeptidyl Peptidase 4