研究动态
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通过可记录条形码的体细胞传递进行克隆谱系追踪揭示了转移性前列腺癌的迁移历史。

Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer.

发表日期:2024 Jul 05
作者: 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
来源: Cancer Discovery

摘要:

原发性肿瘤扩散至转移部位的模式仍知之甚少。在这里,我们使用一种新型的基于注射的小鼠模型 - EvoCaP(前列腺癌的进化)定义了前列腺癌(PCa)的转移播种模式,该模型具有侵袭性转移癌至骨、肝、肺和淋巴结的特征。为了定义原发位点和转移位点之间的迁移历史,我们使用 EvoTraceR 管道来跟踪包含可记录条形码的不同肿瘤克隆。我们在转移性播种中检测到原发肿瘤广泛的瘤内异质性,很少有克隆群(CP)引发大多数迁移。转移到转移的接种并不常见,因为大多数细胞仍然局限于组织内。我们模型中的迁移模式与人类 PCa 播种拓扑一致。我们的研究结果支持这样的观点:转移性前列腺癌是一种全身性疾病,由一波又一波的侵袭性克隆扩大其生态位驱动,很少克服限制,否则它们将被限制在原发或转移部位。
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.