Early and late endothelial response in breast cancer metastasis in mice: simultaneous quantification of endothelial biomarkers using a mass spectrometry-based method.

Abstract

The endothelium plays an important role in cancer metastasis, but the mechanisms involved are still not clear. In the present work, we characterised the changes in endothelial function at early and late stages of breast cancer progression in an orthotopic model of murine mammary carcinoma (4T1 cells). Endothelial function was analysed based on simultaneous microflow liquid chromatography-tandem mass spectrometry using multiple reaction monitoring (microLC/MS-MRM) quantification of 12 endothelium-related biomarkers, including those reflecting glycocalyx disruption - syndecan-1 (SDC-1), endocan (ESM-1); endothelial inflammation - vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin (E-sel); endothelial permeability - fms-like tyrosine kinase 1 (FLT-1), angiopoietin 2 (Angpt-2); and haemostasis - von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), as well as those that are pathophysiologically linked to endothelial function - adrenomedullin (ADM) and adiponectin (ADN). The early phase of metastasis in mouse plasma was associated with glycocalyx disruption (increased SDC-1 and ESM-1), endothelial inflammation [increased soluble VCAM-1 (sVCAM-1)] and increased vascular permeability (Angpt-2). During the late phase of metastasis, additional alterations in haemostasis (increased PAI-1 and vWF), as well as a rise in ADM and substantial fall in ADN concentration, were observed. In conclusion, in a murine model of breast cancer metastasis, we identified glycocalyx disruption, endothelial inflammation and increased endothelial permeability as important events in early metastasis, while the late phase of metastasis was additionally characterised by alterations in haemostasis.

• Authors: Joanna Suraj, Anna Kurpińska, Agnieszka Zakrzewska, Magdalena Sternak, Marta Stojak, Agnieszka Jasztal, Maria Walczak, Stefan Chlopicki
• Journal: Disease models & mechanisms (Dis Model Mech) Vol. 12 Issue 3 (03 01 2019) ISSN: 1754-8411 [Electronic] England
• PMID: 30683749 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019. Published by The Company of Biologists Ltd.

Chemical References

• Biomarkers, Tumor

Topics

• Animals
• Biomarkers, Tumor (blood)
• Blood Cell Count
• Body Weight
• Cell Line, Tumor
• Cell Membrane Permeability
• Endothelial Cells (metabolism)
• Female
• Glycocalyx (metabolism)
• Hemostasis
• Inflammation (blood, pathology)
• Mammary Neoplasms, Animal (blood, pathology)
• Mass Spectrometry (methods)
• Mice, Inbred BALB C
• Organ Size