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Pancreas. 2013 Jul;42(5):861-70. doi: 10.1097/MPA.0b013e318279d568.

The differentiation of pancreatic tumor-initiating cells by vitronectin can be blocked by cilengitide.

Author information

1
Cancer Stem Cell Section, Laboratory of Cancer Prevention, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA. cabarcas002@gannon.edu

Abstract

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.

PMID:
23462327
PMCID:
PMC3676482
DOI:
10.1097/MPA.0b013e318279d568
[Indexed for MEDLINE]
Free PMC Article

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