Molecular, Cellular and Systemic Mechanisms of Breast Cancer Metastasis

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

We extensively characterized the 3D organoid-like culture paradigm (termed, "emboli culture") through transcriptomics, metabolism, and proteomics, which showed that this paradigm is very useful in modeling in vivo tumor architecture. We used this model to investigate how E-cadherin modulates metastatic cancer cell biology and found a signaling pathway to mitochondria and alterations in mitochondrial activity that support cancer cell survival. In preparation to extend these findings to the study of circulating tumor cells that occur in clusters, we developed imaging mass cytometry as a tool to study such cells with minimal processing of the liquid biopsy. The findings from these two lines of research are in preparation for publication. For our investigations of systemic effects of cancer, we determined that CEBPD supports the development of specific immune cells that suppress anti-tumor activity of T-cells or directly combat cancer cells. The signals that modulate these activities are under current investigation. For this, we are also moving to in vitro co-culture assays in organoid-like emboli cultures that mimic lung metastases.