title: Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma.
abstract: 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.
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China.
authors.forename: Saiyin
authors.initials: S
authors.lastname: Hexige
authors.affiliation: Cold Spring Harbor Laboratory, New York, NY11724, United States of America.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Ardito-Abraham
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China.
authors.forename: Youheng
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Cold Spring Harbor Laboratory, New York, NY11724, United States of America.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Cold Spring Harbor Laboratory, New York, NY11724, United States of America.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: Cold Spring Harbor Laboratory, New York, NY11724, United States of America.
authors.forename: Jianang
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, 20032, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yi
authors.affiliation: Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, 44195.|Department of Pathology, The University of Texas MD Anderson Cancer Center.
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.affiliation: Departments of Pharmacology and Oncology, Johns Hopkins School of Medicine, MD 21205, United States of America.
authors.forename: Jun O
authors.initials: JO
authors.lastname: Liu
authors.affiliation: Cold Spring Harbor Laboratory, New York, NY11724, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Tuveson
authors.affiliation: Cold Spring Harbor Laboratory, New York, NY11724, United States of America.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Lou
authors.affiliation: State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D055806:Microvessels / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human
keywords: 3D imaging; basal microvilli; microvessels; neoplasia; pancreas