Abstract
Pancreatic ductal adenocarcinomas are characterized by a complex and robust tumor microenvironment (TME) consisting of fibrotic tissue, excessive levels of hyaluronan (HA), and immune cells. We utilized quantitative multi-parametric magnetic resonance imaging (mp-MRI) methods at 14 Tesla in a genetically engineered KPC (KrasLSL-G12D/+, Trp53LSL-R172H/+, Cre) mouse model to assess the complex TME in advanced stages of tumor development. The whole tumor, excluding cystic areas, was selected as the region of interest for data analysis and subsequent statistical analysis. Pearson correlation was used for statistical inference. There was a significant correlation between tumor volume and T2 (r = -0.66), magnetization transfer ratio (MTR) (r = 0.60), apparent diffusion coefficient (ADC) (r = 0.48), and Glycosaminoglycan-chemical exchange saturation transfer (GagCEST) (r = 0.51). A subset of mice was randomly selected for histological analysis. There were positive correlations between tumor volume and fibrosis (0.92), and HA (r = 0.76); GagCEST and HA (r = 0.81); and MTR and CD31 (r = 0.48). We found a negative correlation between ADC low-b (perfusion) and Ki67 (r = -0.82). Strong correlations between mp-MRI and histology results suggest that mp-MRI can be used as a non-invasive tool to monitor the tumor microenvironment.
Highlights
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA [1]
Pancreatic ductal adenocarcinoma (PDAC), unlike other tumors, displays robust stroma and a dense extracellular matrix (ECM), which is often termed as desmoplasia [2]
We have previously demonstrated effectiveness of mpMRI based approach and found that T2 and magnetization transfer ratio (MTR) were sensitive to increase in fibrotic tissue accumulation [7,8] during the early stages of tumor development
Summary
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA [1]. The higher death rate in pancreatic cancer is partly attributable to the complex nature of the tumor microenvironment (TME), which is difficult to monitor and target using novel therapeutic drugs. Pancreatic ductal adenocarcinoma (PDAC), unlike other tumors, displays robust stroma and a dense extracellular matrix (ECM), which is often termed as desmoplasia [2]. The desmoplasia continuously evolves during the disease progression to include higher numbers of stromal fibroblasts, immune cells, excessive deposition of ECM, and a complex mixture of proteoglycans and glycosaminoglycans (Gag) [3]. PDAC tumor cells produce exceedingly high concentrations of Gag in the tumor interstitium [2,4], which can lead to exceedingly high interstitial fluid pressure (IFP). A clear understanding of TME may help in targeting specific underlying pathophysiological changes and effective delivery of therapeutic drugs to the tumors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
