Desmin expression in colorectal cancer stroma correlates with advanced stage disease and marks angiogenic microvessels

Clinical Proteomics

Jennifer E Hardingham²  Timothy J Price¹  Adrian G Cummins³  Tim Chataway⁴  Gemma Hardi²  Zaipul Izwan²  Georgia Arentz² 

[1] Department of Haematology-Oncology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Medicine, University of Adelaide, , AustraliaDepartment of Haematology-Oncology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Haematology-Oncology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Medicine, University of Adelaide, , AustraliaDepartment of Medicine, University of Adelaide, , AustraliaDepartment of Haematology-Oncology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Medicine, University of Adelaide, , Australia;Department of Haematology-Oncology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Physiology, University of Adelaide, , AustraliaDepartment of Haematology-Oncology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Haematology-Oncology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Physiology, University of Adelaide, , AustraliaDepartment of Physiology, University of Adelaide, , AustraliaDepartment of Haematology-Oncology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Physiology, University of Adelaide, , Australia;Department of Medicine, University of Adelaide, , AustraliaDepartment of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Medicine, University of Adelaide, , AustraliaDepartment of Medicine, University of Adelaide, , AustraliaDepartment of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville, AustraliaDepartment of Medicine, University of Adelaide, , AustraliaDepartment of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville, Australia;Department of Physiology, Flinders University, Bedford Park, AustraliaDepartment of Physiology, Flinders University, Bedford Park, AustraliaDepartment of Physiology, Flinders University, Bedford Park, Australia

关键词: Colorectal cancer;    2D DIGE;    desmin;    biomarker;    pericyte;    angiogenesis;   

DOI  :  10.1186/1559-0275-8-16

来源: Humana Press Inc

【 摘 要 】

Abstract

Introduction

Biomarkers 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.

Methods

Protein 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.

Results

Desmin 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.

Conclusion

Pericyte 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.

【 授权许可】

Unknown