Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; Gallipoli Medical Research, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia.
Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia.
Cell Rep. 2024 Jul 23;43(7):114512. doi: 10.1016/j.celrep.2024.114512. Epub 2024 Jul 13.
Tumor self-seeding is a process whereby circulating tumor cells (CTCs) recolonize the primary tumor, which promotes tumor growth, angiogenesis, and invasion. However, the detailed nature and functions of tumor self-seeded cells (TSCs) have not been well defined due to challenges in tracking and isolating TSCs. Here, we report an accurate animal model using photoconvertible tagging to recapitulate the spontaneous process of tumor self-seeding and identify TSCs as a subpopulation of primary tumor cells with enhanced invasiveness and survival. We demonstrate transmembrane-4-L-six-family-1 (TM4SF1) as a marker of TSCs, which promotes migration, invasion, and anchorage-independent survival in cancer cells. By analyzing single-cell RNA sequencing datasets, we identify a potential TSC population with a metastatic profile in patients with cancer, which is detectable in early-stage disease and expands during cancer progression. In summary, we establish a framework to study TSCs and identify emerging cell targets with diagnostic, prognostic, or therapeutic potential in cancers.
肿瘤自我播种是一个循环肿瘤细胞（CTC）重新殖民原发性肿瘤的过程，它促进肿瘤生长、血管生成和侵袭。然而，由于在追踪和分离 TSC 方面存在挑战，肿瘤自我播种细胞（TSC）的详细性质和功能尚未得到很好的定义。在这里，我们报告了一个使用光转化标记来重现肿瘤自我播种自发过程的精确动物模型，并将 TSC 鉴定为原发性肿瘤细胞的一个亚群，具有增强的侵袭性和存活能力。我们证明跨膜 4 型 L 六家族 1（TM4SF1）是 TSC 的标志物，它促进了癌细胞的迁移、侵袭和锚定非依赖性存活。通过分析单细胞 RNA 测序数据集，我们在癌症患者中鉴定出具有转移特征的潜在 TSC 群体，该群体在早期疾病中可检测到，并在癌症进展过程中扩大。总之，我们建立了一个研究 TSC 的框架，并鉴定出具有诊断、预后或治疗潜力的新兴细胞靶标。
