Mechanisms of Transendothelial Migration of Primary Human Invasive Ductal Carcinoma Cells from ER+, Her2+, and Triple-Negative Disease
Technical Report,01 Sep 2014,31 Aug 2016
Albert Einstein College of Medicine Bronx United States
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The majority of breast cancer related deaths are not due to the primary tumor, but to the metastatic cancer spread to distant sites. The Condeelis lab has been successful in studying dissemination of breast cancer at single cell resolution using newly developed multiphoton imaging tools and mouse models. Their studies have led to the identification of the tumor microenvironment of metastasis or TMEM in mouse and human mammary tumors, sites where transendothelial migration TEM occur and therefore sites of intravasation. The constituent cells of TMEM are an endothelial cell, a perivascular macrophage and an invasive Menaexpressing tumor cell in direct contact. TMEMs are present in human invasive breast tumors and the density of TMEMs is positively associated with the risk of developing metastases. These studies also led to the identification of the Invasion Signature, revealing genes differentially expressed by tumor cells during macrophage dependent migration in the primary tumor. These studies indicate that many of the epigenetic changes observed in invasive mammary cancer cells are clustered in the motility pathways that control actin polymerization, directional cell movement, and the formation of invadopodia.
- Medicine and Medical Research