PMID- 23583653
OWN - NLM
STAT- MEDLINE
DCOM- 20131105
LR  - 20130527
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 182
IP  - 6
DP  - 2013 Jun
TI  - Multiple microvascular alterations in pancreatic islets and neuroendocrine tumors 
      of a Men1 mouse model.
PG  - 2355-67
LID - S0002-9440(13)00201-0 [pii]
LID - 10.1016/j.ajpath.2013.02.023 [doi]
AB  - Vascular therapeutic targeting requires thorough evaluation of the mechanisms 
      activated in the specific context of each particular tumor type. We highlight 
      structural, molecular, and functional microvascular aberrations contributing to 
      development and maintenance of pancreatic neuroendocrine tumors (NETs), with 
      special reference to multiple endocrine neoplasia 1 (MEN1) syndrome, using a Men1 
      mouse model. Tissue samples were analyzed by immunofluorescence to detect vessel 
      density and pericyte distribution within the endocrine pancreas; expression of 
      angiogenic factors was assessed by immunohistochemistry and quantitative 
      real-time PCR in isolated islets and adenomas cultured under normoxic or hypoxic 
      conditions. The increased vascular density of pancreatic NETs developed in Men1 
      mice was paralleled by an early and extensive redistribution of pericytes within 
      endocrine tissue. These morphological alterations are supported by, and in some 
      cases preceded by, fine-tuned variations in expression of several angiogenic 
      regulators and are further potentiated by hypoxia. By combining two novel ex vivo 
      and in vivo single-islet and tumor perfusion techniques, we demonstrated that 
      both vascular reactivity and blood perfusion of tumor arterioles are 
      significantly altered in response to glucose and L-nitro-arginine methyl ester. 
      Our findings unravel multiple potential molecular and physiological targets 
      differentially activated in the endocrine pancreas of Men1 mice and highlight the 
      need for in-depth functional studies to fully understand the contribution of each 
      component to development of pancreatic NETs in MEN1 syndrome.
CI  - Copyright (c) 2013 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Chu, Xia
AU  - Chu X
AD  - Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
FAU - Gao, Xiang
AU  - Gao X
FAU - Jansson, Leif
AU  - Jansson L
FAU - Quach, My
AU  - Quach M
FAU - Skogseid, Britt
AU  - Skogseid B
FAU - Barbu, Andreea
AU  - Barbu A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130412
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Angiogenesis Inducing Agents)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Angiogenesis Inducing Agents/metabolism
MH  - Animals
MH  - Arterioles/physiology
MH  - Disease Models, Animal
MH  - Gene Expression Regulation, Neoplastic
MH  - Islets of Langerhans/*blood supply/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microvessels/pathology
MH  - Multiple Endocrine Neoplasia Type 1/*blood supply/metabolism/pathology
MH  - Neoplasm Proteins/metabolism
MH  - Neovascularization, Pathologic/genetics/metabolism/*pathology
MH  - Pancreatic Neoplasms/*blood supply/metabolism/pathology
MH  - Pericytes/pathology
MH  - Proto-Oncogene Proteins/metabolism
MH  - RNA, Messenger/genetics
EDAT- 2013/04/16 06:00
MHDA- 2013/11/06 06:00
CRDT- 2013/04/16 06:00
PHST- 2012/12/27 00:00 [received]
PHST- 2013/02/04 00:00 [revised]
PHST- 2013/02/12 00:00 [accepted]
PHST- 2013/04/16 06:00 [entrez]
PHST- 2013/04/16 06:00 [pubmed]
PHST- 2013/11/06 06:00 [medline]
AID - S0002-9440(13)00201-0 [pii]
AID - 10.1016/j.ajpath.2013.02.023 [doi]
PST - ppublish
SO  - Am J Pathol. 2013 Jun;182(6):2355-67. doi: 10.1016/j.ajpath.2013.02.023. Epub 
      2013 Apr 12.