Animal Model to Investigate the Potential for Breast Cancer Metastatic Dissemination Following Surgery Intervention on the Primitive Tumor

摘要

This one-year project was aimed to establish a new animal model and generate preliminary data with the ultimate goal of ascertaining whether the post-operative tissue microenvironment, caused by breast conserving surgery, promotes metastatic dissemination. We engineered 4T1 murine mammary breast cancer cells to express either enhanced Green Fluorescent protein (eGFP) or Dendra2 green-to-red photoswitchable fluorescent protein. Furthermore, we established a mouse model of partial and complete resection of mammary tumors. Among the genes that we believe will be altered in breast cancer cells by the postoperative stroma is CX3CR1, the sole receptor for the chemokine fractalkine (CX3CL1). We therefore investigated the role of this receptor in the metastatic dissemination of breast cancer to the skeleton and described for the first time its crucial role in cancer cell adhesion to bone marrow endothelium and extravasation into the bone stroma.