Identification of Vascular Breast Tumor Markers by Laser Capture Microdissection and Label-Free LC-MS.

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DOIResolve DOI: http://doi.org/10.1021/pr101267k
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TypeArticle
Journal titleJournal of Proteome Research
Volume10
Issue5
Pages24792493; # of pages: 15
Subjectcancer; vessels; laser capture microdissection; invasive ductal carcinoma
AbstractBlood vessels in tumors frequently show abnormal characteristics, such as tortuous morphology or leakiness, but very little is known about protein expression in tumor vessels. In this study, we have used laser capture microdissection (LCM) to isolate microvessels from clinical samples of invasive ductal carcinoma (IDC), the most common form of malignant breast cancer, and from patient-matched adjacent nonmalignant tissue. This approach eliminates many of the problems associated with the heterogeneity of clinical tumor tissues by controlling for differences in protein expression between both individual patients and different cell types. Proteins from the microvessels were trypsinized and the resulting peptides were quantified by a label-free nanoLC−MS method. A total of 86 proteins were identified that are overexpressed in tumor vessels relative to vessels isolated from the adjacent nonmalignant tissue. These proteins include well-known breast tumor markers such as Periostin and Tenascin C but also proteins with lesser-known or emerging roles in breast cancer and tumor angiogenesis (i.e., Serpin H1, Clic-1, and Transgelin 2). We also identified 40 proteins that were relatively under-expressed in IDC tumor vessels, including several components of the basement membrane whose lower expression could be responsible for weakening tumor vessels. Lastly, we show that a subset of 29 proteins, derived from our list of differentially expressed proteins, is able to predict survival in three publicly available clinical breast cancer microarray data sets, which suggests that this subset of proteins likely plays a functional role in cancer progression and outcome.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; NRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedYes
NPARC number19105356
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Record identifier230c95eb-0af9-4328-816e-4cfb4e812fa9
Record created2011-12-20
Record modified2016-05-09
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