Chronic cadmium exposure in vitro causes acquisition of multiple tumor cell characteristics in human pancreatic epithelial cells.

作者: Wei Qu , Erik J. Tokar , Andrew J. Kim , Matthew W. Bell , Michael P. Waalkes

DOI: 10.1289/EHP.1205082

关键词:

摘要: Background: Cancer may be a stem cell (SC)–based disease involving formation of cancer SCs (CSCs) potentially arising from transformation normal SCs. Cadmium has been linked to human pancreatic cancer. Objective: We studied cadmium exposure ductal epithelial (HPDE) cells and whether targeted in this process. Methods: chronically exposed HPDE low level (1 μM) for ≤ 29 weeks. Nonadherent spheroid was used indicate CSC-like production, we assessed tumor characteristics such spheres. Assessed including secretion matrix metalloproteinase-9 (MMP-9), invasion, colony were fortified by evaluating expression relevant genes real-time reverse transcription polymerase chain reaction Western blot. Results: Increased MMP-9 overexpression the marker S100P occurred chronic (29 weeks exposure) cadmium-exposed (CCE) cells. CCE also showed markedly higher typical Floating “spheres” viable cells, known contain an abundance or CSCs, form vitro with many types. produced 3-fold more spheres than control invasive, secreted MMP-9, overexpressed markers SCs/CSCs (i.e., CXCR4, OCT4, CD44) S100P, cancer. CCE-derived rapidly aggressive, highly branched, poorly differentiated glandular-like structures Matrigel. Conclusions: Chronic multiple cell–derived These data support plausibility as carcinogen.

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