Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma.

Autor: Hexige S; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China., Ardito-Abraham CM; Cold Spring Harbor Laboratory, New York, NY11724, United States of America., Wu Y; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China., Wei Y; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China., Fang Y; Cold Spring Harbor Laboratory, New York, NY11724, United States of America., Han X; Cold Spring Harbor Laboratory, New York, NY11724, United States of America., Li J; Cold Spring Harbor Laboratory, New York, NY11724, United States of America., Zhou P; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China., Yi Q; General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, 20032, People's Republic of China., Maitra A; Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, 44195.; Department of Pathology, The University of Texas MD Anderson Cancer Center., Liu JO; Departments of Pharmacology and Oncology, Johns Hopkins School of Medicine, MD 21205, United States of America., Tuveson DA; Cold Spring Harbor Laboratory, New York, NY11724, United States of America., Lou W; Cold Spring Harbor Laboratory, New York, NY11724, United States of America., Yu L; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2015 Jun; Vol. 236 (2), pp. 142-154. Date of Electronic Publication: 2015 Feb 17.
DOI: 10.1002/path.4506
Abstrakt: Pancreatic ductal adenocarcinoma (PDAC) is a nearly lethal neoplasm. It is a remarkably stroma-rich, vascular-poor and hypo-perfused tumour, which prevents efficient drug delivery. Paradoxically, the neoplastic cells have robust glucose uptake, suggesting that the microvasculature has adopted an alternative method for nutrient uptake and cellular trafficking. Using adapted thick tumour section immunostaining and three-dimensional (3D) construction imaging in human tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumours; long, hair-like projections on the basal surface of microvessels that we refer to as 'basal microvilli'. Functionally, these basal microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties, and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as demonstrated by PET-CT, the tumour microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumour itself. In addition, these basal microvilli were found in regions of the tumour with low GLUT-1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumour milieu. Similar microvasculature features were also observed in a K-Ras-driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature. Because basal microvilli are pathological features with endo- and exocytic properties, they may provide a non-conventional method for cellular trafficking in PDAC tumours.
(Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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