Journal of Clinical Toxicology
Open Access

Arsenic-induced acquisition of cancer stem cell-like characteristics during malignant transformation of human pancreatic epithelial ductal cells

4^th Global Summit on Toxicology

August 24-26, 2015 Philadelphia, USA

Wei Qu

Posters-Accepted Abstracts: J Clin Toxicol

Abstract :

Emerging data indicates cancer stem cells (CSCs) may be critical to the carcinogenic process. Arsenic is linked with human
pancreatic diseases potentially including cancer. Our prior work showed chronic cadmium exposure of a human pancreatic
ductal epithelial (HPDE) cell line caused oncogenic transformation and formation of CSC-like cells. Thus, we studied if inorganic
arsenic exposure could induce a similar tumor cell phenotype in HPDE cells and derivative non-adherent spheroids, which are
enriched in stem cells (SCs or CSCs). HPDE cells were chronically exposed to sodium arsenite (2.5 μM) for up to 30 weeks and
cancer cell characteristics were assessed including matrix metalloproteinase-9 (MMP-9) secretion, invasion, colony formation and
expression of cancer relevant genes by RT-PCR or immunoblotting. Non-adherent spheroid formation was used to assess CSClike
production and tumor cell phenotype was assessed in such spheres. Chronic arsenic exposed (CAE) cells (30 weeks) showed
morphological changes (loss of contact inhibition, atypical foci of cell mounding), increased MMP-9 secretion and colony formation,
and marked over-expression of pancreatic cancer markers (S100P, PSCA), oncogenes (C-myc, C-jun), and the cell proliferation marker
Cyclin D1, all typical for pancreatic cancer cells. CAE cells also became tolerant to arsenic (LC50 74.8±1.9 μM) compared to control
(18.1±2.1 μM) which is common in chronic treatment. Compared to control, CAE cells produced 300% more non-adherent spheres,
which contain an abundance of SCs or CSCs. CAE-derived spheres were more invasive, secreted more MMP-9, and over-expressed
markers for pancreatic CSCs (CXCR4, CD133, CD44) and S100P. Single spheres from CAE cells rapidly produced aggressive, highly
branched, poorly differentiated glandular-like structures in Matrigel. Thus, chronic arsenic causes acquisition of multiple tumor cell
characteristics in HPDE cells. These data support the plausibility of arsenic as a human pancreatic carcinogen.