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Vascular patterning and permeability in prostate cancer models with differing osteogenic properties
Author(s) -
Dafni Hagit,
Burghardt Andrew J.,
Majumdar Sharmila,
Navone Nora M.,
Ronen Sabrina M.
Publication year - 2012
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1800
Subject(s) - prostate cancer , medicine , vascular permeability , pathology , bone metastasis , metastasis , prostate , bone marrow , cancer
Bone metastasis is a major cause of morbidity and mortality in prostate cancer. However, the lack of clinically relevant models hinders our understanding of the disease as well as development of effective therapies and imaging approaches. We used noninvasive MRI, histology and micro CT to further characterize the newly established prostate cancer bone metastases‐derived model MDA‐PCa‐118b, and to compare it to the well‐established PC‐3MM2 model with regard to bone structure and vascular patterning. The PC‐3MM2 model is highly osteolytic whereas the MDA‐PCa‐118b model shows a robust osteoblastic reaction, as often seen in clinical cases. Macromolecular contrast enhanced MRI revealed differences in vascular permeability patterns, which appeared peripheral for PC‐3MM2 and nodular for MDA‐PCa‐118b, matching the microscopic cellular composition of each model: PC‐3MM2 exclusively recruits endothelial cells to form thin tumor‐core blood vessels and enlarged, leaky peripheral vessels, whereas MDA‐PCa‐118b also recruits bone‐forming cells and pericytes such that small tumor nests are encircled with leaky vessels and embedded in bone‐like tissue dotted with pericyte‐covered vessels. Despite these structural differences, vascular permeability was reduced in both tumor models by either imatinib or SU10944 treatment. This study highlights the importance of clinically relevant osteogenic models of human prostate cancer and the value of such models not only in enhancing our understanding of tumorigenesis, metastasis and response to therapy, but also for development of appropriate methods for noninvasive imaging of these processes. Copyright © 2011 John Wiley & Sons, Ltd.