TM4SF1+肿瘤自播种细胞的鉴定与特征分析

Identification and characterization of TM4SF1+ tumor self-seeded cells

Cell Reports

影响因子:6.9

分区:生物学1区 Top / 细胞生物学2区

发表日期:2024 Jul 23

作者: Haotian Yang, Haolu Wang, Yaowu He, Yang Yang, Erik W Thompson, Di Xia, Leslie J Burke, Lu Cao, John D Hooper, Michael S Roberts, Darrell H G Crawford, Xiaowen Liang

DOI: 10.1016/j.celrep.2024.114512

摘要

肿瘤自播种是一种血流循环肿瘤细胞（CTCs）重新定殖原发肿瘤的过程，促进肿瘤生长、血管生成和侵袭。然而，由于追踪和分离TSCs的难题，肿瘤自播种细胞（TSCs）的详细性质和功能尚未明确。在此，我们报道了一种利用光可变标记技术的精确动物模型，以再现肿瘤自播种的自然过程，并将TSCs鉴定为具有增强侵袭性和存活能力的原发肿瘤细胞亚群。我们证明了跨膜蛋白-4-L-六家族-1（TM4SF1）作为TSCs的标志物，能促进癌细胞的迁移、侵袭和无锚定存活。通过分析单细胞RNA测序数据集，我们识别出具有转移特征的潜在TSC群体，在早期疾病中可检测到，并在肿瘤进展过程中扩展。总之，我们建立了研究TSCs的框架，并鉴定出具有诊断、预后或治疗潜力的新兴细胞靶点。

Abstract

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.