cxcr4cxcl12 participate in extravasation of metastasizing breast cancer cells within the liver in a rat modelcxcr4cxcl12参与溢出肝内转移的乳腺癌细胞的大鼠模型.pdfVIP

CXCR4/CXCL12 Participate in Extravasation of Metastasizing Breast Cancer Cells within the Liver in a Rat Model 1. ´ 1. 1 ¨ 1 Claudia Wendel , Andre Hemping-Bovenkerk , Julia Krasnyanska , Soren Torge Mees , Marina 2 1 ¨ 3 Kochetkova , Sandra Stoeppeler , Jorg Haier * 1 Department of General and Visceral Surgery, University Hospital Muenster, Muenster, Germany, 2 Chemokine Biology Division, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia, 3 Comprehensive Cancer Center Muenster, University Hospital Muenster, Muenster, Germany Abstract Introduction: Organ-specific composition of extracellular matrix proteins (ECM) is a determinant of metastatic host organ involvement. The chemokine CXCL12 and its receptor CXCR4 play important roles in the colonization of human breast cancer cells to their metastatic target organs. In this study, we investigated the effects of chemokine stimulation on adhesion and migration of different human breast cancer cell lines in vivo and in vitro with particular focus on the liver as a major metastatic site in breast cancer. Methods: Time lapse microscopy, in vitro adhesion and migration assays were performed under CXCL12 stimulation. Activation of small GTPases showed chemokine receptor signalling dependence from ECM components. The initial events of hepatic colonisation of MDA-MB-231 and MDA-MB-468 cells were investigated by intravital microscopy of the liver in a rat model and under shRNA inhibition of CXCR4. Results: In vitro, stimulation with CXCL12 induced increased chemotactic cell motility (p,0.05). This effect was dependent on a