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Abstract IA014: Regulation of disseminated tumor cell dormancy in brain by the perivascular niche

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.