Journal
PANCREAS
Volume 42, Issue 5, Pages 861-870Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0b013e318279d568
Keywords
pancreatic cancer; TICs; vitronectin; differentiation; Cilengitide
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Funding
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
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Objective: Pancreatic cancer is a leading cancer type and its molecular pathology is poorly understood. The only potentially curative therapeutic option available is complete surgical resection; however, this is inadequate as most of the patients are diagnosed at an advanced or metastatic stage. Tumor-initiating cells (TICs) constitute a subpopulation of cells within a solid tumor that sustain tumor growth, metastasis, and chemo/radioresistance. Within pancreatic cancer, TICs have been identified based on the expression of specific cell surface markers. Methods: We use a sphere formation assay to enrich putative TICs and use human serum as a driver of differentiation. We demonstrate by using specific blocking reagents that we can inhibit the differentiation process and maintain TIC-associated markers and genes. Results: We can induce differentiation of pancreatospheres with the addition of human serum, and we identified vitronectin as an inducer of differentiation. We inhibit differentiation by human serum using an arginine-glycine-aspartate-specific peptide, which is Cilengitide; hence, demonstrating this differentiation is mediated via specific integrin receptors. Conclusions: Overall, our studies further the definition of pancreatic TICs and provide further insight into both the maintenance and differentiation of this lethal population.
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