Serio, Ryan N, Scheben, Armin, Lu, Billy, Gargiulo, Domenic V, Patruno, Lucrezia, Buckholtz, Caroline L, Chaffee, Ryan J, Jibilian, Megan C, Persaud, Steven G, Staklinski, Stephen J, Hassett, Rebecca, Brault, Lise M, Ramazzotti, Daniele, Barbieri, Christopher E, Siepel, Adam C, Nowak, Dawid G (July 2024) Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer. Cancer Discovery. ISSN 2159-8274
Abstract
The patterns by which primary tumors spread to metastatic sites remain poorly understood. Here, we define patterns of metastatic seeding in prostate cancer (PCa) using a novel injection-based mouse model - EvoCaP (Evolution in Cancer of the Prostate), featuring aggressive metastatic cancer to bone, liver, lungs, and lymph nodes. To define migration histories between primary and metastatic sites, we used our EvoTraceR pipeline to track distinct tumor clones containing recordable barcodes. We detected widespread intratumoral heterogeneity from the primary tumor in metastatic seeding, with few clonal populations (CPs) instigating most migration. Metastasis-to-metastasis seeding was uncommon, as most cells remained confined within the tissue. Migration patterns in our model were congruent with human PCa seeding topologies. Our findings support the view of metastatic PCa as a systemic disease driven by waves of aggressive clones expanding their niche, infrequently overcoming constraints that otherwise keep them confined in the primary or metastatic site.
| Item Type: | Paper |
|---|---|
| Subjects: | diseases & disorders > cancer diseases & disorders diseases & disorders > cancer > cancer types > prostate cancer diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL labs > Siepel lab School of Biological Sciences > Publications |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 5 July 2024 |
| Date Deposited: | 08 Jul 2024 13:11 |
| Last Modified: | 10 Dec 2024 15:49 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41596 |
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