TM4SF1+肿瘤自种子细胞的识别和表征
Identification and characterization of TM4SF1+ tumor self-seeded cells
影响因子:6.90000
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
摘要
肿瘤自种是一个过程，从而使肿瘤细胞（CTC）重新殖民循环原发性肿瘤，从而促进肿瘤生长，血管生成和侵袭。但是，由于跟踪和分离TSC的挑战，肿瘤自种细胞（TSC）的详细性质和功能尚未得到很好的定义。在这里，我们报告了使用可光转换标签的精确动物模型，以概括肿瘤自种的自发过程，并将TSC识别为具有侵入性和存活率的原代肿瘤细胞的亚群。我们证明了TRANSMBRANE-4-L-SIX-FAMILY-1（TM4SF1）作为TSC的标记，可促进癌细胞中迁移，侵袭和非锚定的生存。通过分析单细胞RNA测序数据集，我们确定了癌症患者具有转移性特征的潜在TSC种群，这在早期疾病中可检测到，并在癌症进展过程中扩展。总而言之，我们建立了一个研究TSC的框架，并确定癌症中具有诊断，预后或治疗潜力的新兴细胞靶标。
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.