Abstract:
BACKGROUND:Cancer may be a stem cell (SC)-based disease involving formation of cancer SCs (CSCs) potentially arising from transformation of normal SCs. Cadmium has been linked to human pancreatic cancer. OBJECTIVE:We studied cadmium exposure of human pancreatic ductal epithelial (HPDE) cells and whether SCs may be targeted in this process. METHODS:We chronically exposed HPDE cells to low level cadmium (1 μM) for ≤ 29 weeks. Nonadherent spheroid formation was used to indicate CSC-like cell production, and we assessed tumor cell characteristics in such spheres. Assessed tumor cell characteristics including secretion of matrix metalloproteinase-9 (MMP-9), invasion, and colony formation were fortified by evaluating expression of relevant genes by real-time reverse transcription polymerase chain reaction and by Western blot. RESULTS:Increased MMP-9 secretion and overexpression of the pancreatic cancer marker S100P occurred in chronic (29 weeks of exposure) cadmium-exposed (CCE) cells. CCE cells also showed markedly higher colony formation and invasion, typical of cancer cells. Floating "spheres" of viable cells, known to contain an abundance of normal SCs or CSCs, form in vitro with many cell types. CCE cells produced 3-fold more spheres than control cells and were more invasive, secreted more MMP-9, and overexpressed markers for pancreatic SCs/CSCs (i.e., CXCR4, OCT4, CD44) and S100P, a marker for pancreatic cancer. CCE-derived spheres rapidly produced aggressive, highly branched, and poorly differentiated glandular-like structures in Matrigel. CONCLUSIONS:Chronic cadmium exposure produced multiple tumor cell characteristics in HPDE cells and CCE cell-derived spheres. These data support the plausibility of cadmium as a human pancreatic carcinogen.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Qu W,Tokar EJ,Kim AJ,Bell MW,Waalkes MPdoi
10.1289/ehp.1205082subject
Has Abstractpub_date
2012-09-01 00:00:00pages
1265-71issue
9eissn
0091-6765issn
1552-9924journal_volume
120pub_type
杂志文章abstract:BACKGROUND:Organophosphorus pesticides (OPs) are developmental neurotoxicants but also produce lasting effects on metabolism. OBJECTIVES/METHODS:We administered diazinon (DZN) or parathion (PRT) to rats on postnatal days 14 at doses straddling the threshold for systemic signs of exposure and assessed the effects on he...
journal_title:Environmental health perspectives
pub_type: 杂志文章
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更新日期:2010-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.9337
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更新日期:1981-01-01 00:00:00
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更新日期:1993-10-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:1998-03-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:2014-03-01 00:00:00
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更新日期:2006-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:1983-11-01 00:00:00
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更新日期:2008-12-01 00:00:00
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更新日期:2012-12-01 00:00:00
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更新日期:1985-10-01 00:00:00
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更新日期:2000-03-01 00:00:00
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journal_title:Environmental health perspectives
pub_type: 杂志文章,评审
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更新日期:1978-08-01 00:00:00
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journal_title:Environmental health perspectives
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doi:10.1289/ehp.5799
更新日期:2003-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1289/ehp.0901200
更新日期:2010-03-01 00:00:00
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更新日期:1998-12-01 00:00:00
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更新日期:2019-10-01 00:00:00
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更新日期:2010-10-01 00:00:00
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journal_title:Environmental health perspectives
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更新日期:2020-11-01 00:00:00