Desmin expression in colorectal cancer stroma correlates with advanced stage disease and marks angiogenic microvesselsReportar como inadecuado




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Clinical Proteomics

, 8:16

First Online: 05 December 2011Received: 21 November 2011Accepted: 05 December 2011

Abstract

IntroductionBiomarkers that improve stratification of colorectal cancer patients for adjuvant therapy versus resection alone, or that are predictive of response to therapeutic agents, have the potential to greatly improve patient selection for such therapies. The aim was to determine proteins differentially expressed within the malignant epithelial glands and closely associated stromal elements compared to matched normal mucosa, and to characterise the over-expression of one such protein as a potential biomarker.

MethodsProtein from laser microdissected tumor and normal mucosa was analysed by two dimensional difference gel electrophoresis 2D DIGE and mass spectrometry to determine differentially over expressed tumor proteins. Tumor over-expression of one such protein, desmin, was quantified using immunofluorescence staining in a larger cohort. Dual staining for desmin and vimentin, or desmin and von Willebrand factor, was performed to determine the cell type of interest.

ResultsDesmin expression was significantly increased between stage I and III tumors, P < 0.0001, and stage II and III tumors, P < 0.0001. Strong focal desmin expression was found in stroma directly adjacent to carcinomatous glands and microvessels. These cells showed co-localisation of desmin and vimentin in close association with cells expressing VWF, indicating they were pericytes. Significantly higher levels of desmin-positive pericytes were observed in late stage tumors, consistent with increased angiogenesis.

ConclusionPericyte coverage of vasculature is a marker of vessel maturation, hence desmin expression may have use as a marker for microvessel maturation. Clinical trials will be needed to determine its use in identifying tumors that will be less responsive to anti-angiogenic therapy.

KeywordsColorectal cancer 2D DIGE desmin biomarker pericyte angiogenesis List of abbreviationsCRCcolorectal cancer

2D DIGE2 dimensional difference gel electrophoresis

MSmass spectrometry

LMDlaser microdissection

VWFvon Willebrand Factor

IFimmunofluorescence

CANacetonitrile.

Electronic supplementary materialThe online version of this article doi:10.1186-1559-0275-8-16 contains supplementary material, which is available to authorized users.

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Autor: Georgia Arentz - Tim Chataway - Timothy J Price - Zaipul Izwan - Gemma Hardi - Adrian G Cummins - Jennifer E Hardingham

Fuente: https://link.springer.com/



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