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Bone Marrow-Derived Progenitor Cells Could Modulate Pancreatic Cancer Tumorigenesis via Peritumoral Microenvironment in a Rat Model

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Abstract:

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.

Keywords: Bone marrow; Microenvironment; Pancreatic cancer; Progenitor cell; Tumorigenesis

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504009788428424

Publication date: January 1, 2009

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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