CMX_SEMINAR（神戸大学CMX創発医学講演会/大学院講義）

Biomarkers of endothelial dysfunction inmice model of breast cancer metastasis＜乳がんマウスにおける内皮機能不全のバイオマーカー＞

Speaker: Prof. Maria Walczak
がん転移における血管内皮の意義に注目した、薬学スペシャリスト
による 、初期のがん（特に転移性乳がん）の血管内皮バイオメー
カーの診断・予後判定指標として果たす役割についてのご講演です。

日時 ： 2022. 12. 6（火） 17:30-19:00
オンライン開催
ZOOM URL : https://kobe-u-acjp.zoom.us/j/84352152283?pwd=VUh6Q0NaUGhZTVNSSThGNnNneVVLdz09

ミーティングID: 843 5215 2283
パスコード: 723125
Abstract:
In recent years, attention has been focused on the significance of the vascular endothelium in cancer metastasis.
Healthy endothelial cells inhibit tumour cell adhesion, transmigration and metastasis formation, whereasendothelial dysfunction, characterised by a shift towards decreased synthesis of vasoprotective mediators andactivation of pro-inflammatory and pro-thrombotic molecules, promotes cancer metastasis. Given the key role ofthe endothelium in metastasis formation we characterise changes in endothelial function that take place during theearly and late phases of breast cancer development in mice by simultaneous determination of secreted proteins,
receptors or cleaved surface proteins circulating in plasma, e.g. syndecan-1, endocan, vascular cell adhesion
molecule, intercellular adhesion molecule 1, E-selectin, fms-like tyrosine kinase 1, angiopoietin 2, von Willebrandfactor, tissue plasminogen activator, plasminogen activator inhibitor 1, adrenomedullin and adiponectin. In ourstudy we use targeted metabolomics and lipidomics for finding a relationship between pathological characteristics
of breast cancer and metabolites of the arginine pathway, glucose metabolism, and structural and signalling lipids inthe early and late stages of murine breast cancer metastasis. Alterations in lipid composition and abundance havebeen established as a hallmark of cancer aggressiveness that may strongly influence the signal transduction process
upon conversion into bioactive lipid mediators, e.g. eicosanoids.
References:
1. . Kij A, Mateuszuk L, Sitek B, Przyborowski K, Zakrzewska A, Wandzel K, Walczak M, Chlopicki S: Simultaneous quantification of PGI2 and TXA2
metabolites in plasma and urine in NO-deficient mice by a novel UHPLC/MS/MS method. J Pharm Biomed Anal. 2016 Sep 10;129:148-154. doi:
10.1016/j.jpba.2016.06.050.
2. Kus K, Kij A, Zakrzewska A, Jasztal A, Stojak M, Walczak M, Chlopicki S: Alterations in arginine and energy metabolism, structural and signalling
lipids in metastatic breast cancer in mice detected in plasma by targeted metabolomics and lipidomics. Breast Cancer Res. 2018 Dec 4;20(1):148.
doi: 10.1186/s13058-018-1075-y.
3. Suraj J, Kurpińska A, Zakrzewska A, Sternak M, Stojak M, Jasztal A, Walczak M, Chlopicki S: Early and late endothelial response in breast cancer
metastasis in mice: simultaneous quantification of endothelial biomarkers using a mass spectrometry-based method. Dis Model Mech. 2019 Mar
1;12(3):dmm036269. doi: 10.1242/dmm.036269.
4. Kurpińska A, Suraj J, Bonar E, Zakrzewska A, Stojak M, Sternak M, Jasztal A, Walczak M: Proteomic characterization of early lung response tobreast cancer metastasis in mice. Exp Mol Pathol. 2019 Apr;107:129-140. doi: 10.1016/j.yexmp.2019.02.001.

Introducing the speaker (Self-introduction):
Maria Walczak has graduated at the Faculty of Pharmacy, Medical Academy in
Krakow (Poland). She received her PhD degree and habilitation at the Faculty ofPharmacy, Jagiellonian University Medical College (UJ CM). Currently she is ahead of the Chair and Department of Toxicology at the Faculty of Pharmacy UJ
CM and a group leader at the Jagiellonian Centre for Experimental Therapeutics(JCET, UJ). Her research primaly focuses on the pharmacokinetic andtoxicokinetic studies of bioactive compounds, metabolite identification,assessment of drug protein binding - subsequently crucial for drugdevelopment. At the core of her work stands the bioanalysis of biomarkers
related to civilisation deseases, as prognostic and diagnostic targets using mass
spectrometry-based methods. She is a specialist in clinical pharmacy.

Coordinator: 教授・島扶美（担当：創薬科学 内線：6582）
Organizer:メディカルトランスフォーメーション研究センター
Contact: 研究支援課研究企画係
E-mail: k9shien@med.kobe-u.ac.jp（内線:5195/5189 ）