LAUSR

The brain provides compelling evidence that tumour dormancy is not simply an intriguing biological phenomenon. Given effective therapy, it may emerge as a culprit of lethality. To date, the mechanism by which the brain microenvironment drives disseminated tumor cells (DTCs) into a dormant state remain elusive. Here, I describe our studies leveraging serial intravital imaging to demonstrate that a large fraction of disseminated breast tumor cells within brain persist as single cells, and that every one of these cells is physically associated with microvasculature. Despite occupying a vascular niche, however, the burden for enforcing dormancy does not lie with endothelium. Instead, perivascular astrocytes are the dominant effector. Specifically, we show that astrocytic laminin-211 signals through DTC dystroglycan to suppress proliferation. Transcriptomic data suggest quiescence may ultimately be driven by sequestration of the Hippo effector yes-associated protein. We view these findings as a first step towards therapies that maintain DTC dormancy to prevent brain metastasis. Citation Format: Cyrus M. Ghajar. Regulation of disseminated tumor cell dormancy in brain by the perivascular niche [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA014.