通过体细胞传递可记录条形码进行克隆系谱追踪,揭示转移性前列腺癌的迁移历史。

IF 29.7 1区 医学 Q1 ONCOLOGY Cancer discovery Pub Date : 2024-10-04 DOI:10.1158/2159-8290.CD-23-1332
Ryan N Serio, Armin Scheben, Billy Lu, Domenic V Gargiulo, Lucrezia Patruno, Caroline L Buckholtz, Ryan J Chaffee, Megan C Jibilian, Steven G Persaud, Stephen J Staklinski, Rebecca Hassett, Lise M Brault, Daniele Ramazzotti, Christopher E Barbieri, Adam C Siepel, Dawid G Nowak
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引用次数: 0

摘要

人们对原发性肿瘤向转移部位扩散的模式仍然知之甚少。在这里,我们利用一种新型注射小鼠模型--EvoCaP(前列腺癌进化),确定了前列腺癌(PCa)的转移播种模式,该模型的特点是侵袭性癌症向骨、肝、肺和淋巴结转移。为了确定原发部位和转移部位之间的迁移历史,我们使用 EvoTraceR 管道追踪含有可记录条形码的不同肿瘤克隆。我们在转移播种中检测到了原发肿瘤广泛的瘤内异质性,少数克隆群(CP)引发了大部分迁移。转移瘤之间的播种并不常见,因为大多数细胞仍局限在组织内。我们模型中的迁移模式与人类 PCa 的播种拓扑结构一致。我们的研究结果支持这样一种观点,即转移性 PCa 是一种由侵袭性克隆波驱动的系统性疾病,它们不断扩大自己的生态位,很少能克服使它们局限在原发或转移部位的限制因素。
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Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer.

The patterns by which primary tumors spread to metastatic sites remain poorly understood. Here, we define patterns of metastatic seeding in prostate cancer 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 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 prostate cancer seeding topologies. Our findings support the view of metastatic prostate cancer 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. Significance: Defining the kinetics of prostate cancer metastasis is critical for developing novel therapeutic strategies. This study uses CRISPR/Cas9-based barcoding technology to accurately define tumor clonal patterns and routes of migration in a novel somatically engineered mouse model (EvoCaP) that recapitulates human prostate cancer using an in-house developed analytical pipeline (EvoTraceR).

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来源期刊
Cancer discovery
Cancer discovery ONCOLOGY-
CiteScore
22.90
自引率
1.40%
发文量
838
审稿时长
6-12 weeks
期刊介绍: Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.
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