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Published on: November 19, 2019
Exocrine pancreatic carcinogenesis and autotaxin expression
Sandeep Kadekar1, Ilona Silins, Anna Korhonen
1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Plos One
|September 7, 2012
Summary
Environmental chemicals can cause pancreatic cancer, particularly in male rats. Autotaxin (ATX), an inflammatory protein, is a key target for these chemicals, suggesting new biomarkers for pancreatic cancer risk.
Area of Science:
- Toxicology
- Oncology
- Biochemistry
Background:
- Exocrine pancreatic cancer has a high mortality rate, with environmental factors suspected but lacking epidemiological support and biomarkers.
- Current understanding of chemical carcinogens targeting the pancreas is limited.
Purpose of the Study:
- To identify common traits of chemicals that induce pancreatic tumors.
- To investigate potential biomarkers for chemical-induced pancreatic carcinogenesis.
Main Methods:
- Analysis of the National Toxicology Program (NTP) bioassay database for chemicals causing pancreatic tumors in rats.
- Text mining of scientific literature to identify suggested modes of action (MOA).
- In vitro cell studies to assess the effects of identified chemicals on inflammatory markers and cell behavior.
Main Results:
- Eight chemicals were identified as inducing exocrine pancreatic tumors exclusively in male rats.
- Inflammatory responses, specifically increased autotaxin (ATX) protein levels, were a common feature.
- Chemicals induced MMP-9 and invasive migration, consistent with ATX activation. Testosterone also increased ATX levels.
Conclusions:
- Autotaxin (ATX) is a molecular target for chemicals that promote pancreatic tumor development in rats.
- ATX and its product lysophosphatidic acid are implicated in human pancreatic cancer, potentially driving invasive growth and metastasis.
- ATX may interact with hormonal pathways or genetic alterations common in pancreatic cancer.
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