Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer.

ABSTRACT:

Objective

Pancreatic ductal adenocarcinoma (PDA) is characterised by stromal desmoplasia and vascular dysfunction, which critically impair drug delivery. This study examines the role of an abundant extracellular matrix component, the megadalton glycosaminoglycan hyaluronan (HA), as a novel therapeutic target in PDA.

Methods

Using a genetically engineered mouse model of PDA, the authors enzymatically depleted HA by a clinically formulated PEGylated human recombinant PH20 hyaluronidase (PEGPH20) and examined tumour perfusion, vascular permeability and drug delivery. The preclinical utility of PEGPH20 in combination with gemcitabine was assessed by short-term and survival studies.

Results

PEGPH20 rapidly and sustainably depleted HA, inducing the re-expansion of PDA blood

SUBMITTER: Jacobetz MA 

PROVIDER: S-EPMC3551211 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature