Abstract A01: Investigating clonal heterogeneity and transcriptional vulnerabilities in latent metastasis

Most cancer deaths are due to the poorly understood process of metastasis, which is seeded by disseminated tumor cells (DTCs). DTCs exhibit exceedingly variable latency, outgrowing immediately or lying dormant for months to years in a viable state of mass dormancy or replicative quiescence. The mechanisms enabling DTCs to survive and resist therapy are poorly understood. We have recently derived several models of latent metastasis that default to a slow-cycling state under stress, reserve the capacity for tumor-initiation, and evade immune surveillance. These DTCs resemble progenitor stem cell populations at the molecular level, actively inhibiting the pro-differentiation Wnt pathway and over-expressing Sox transcriptional factors. Tissue immunofluorescence demonstrates that latent DTCs typically manifest as solitary or clusters of infiltrating cancer cells without forming overt metastasis within several months after hematogenous dissemination in mice. This compelling observation begs the question, are these bursts truly monoclonal?Recent studies have shown that rapidly cycling DTCs occasionally migrate in groups and this improves their likelihood of establishing polyclonal metastases; however, we hypothesize that colonization in the context of delayed metastasis may in fact be monoclonal. To address this question, unique and heritable fluorescent markers were integrated into the host genome of isolated DTCs to interrogate the clonal dynamics of apparent proliferative bursts ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Niche / Cellular Interactions: Poster Presentations - Proffered Abstracts Source Type: research