Identification and characterization of TM4SF1+ tumor self-seeded cells

• Published in: Cell reports (Cambridge) Vol. 43; no. 7; p. 114512
• Main Authors: Yang, Haotian, Wang, Haolu, He, Yaowu, Yang, Yang, Thompson, Erik W., Xia, Di, Burke, Leslie J., Cao, Lu, Hooper, John D., Roberts, Michael S., Crawford, Darrell H.G., Liang, Xiaowen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.07.2024; Elsevier
• Subjects: Animals; Antigens, Surface; Biomarkers, Tumor - metabolism; Cell Line, Tumor; Cell Movement; cell population; CP: Cancer; Humans; invasion; liver cancer; Mice; Neoplasm Invasiveness; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Neoplastic Cells, Circulating - metabolism; Neoplastic Cells, Circulating - pathology; photoconvertible tagging; TM4SF1; tumor self-seeded cells; tumor self-seeding; tumor self-seeding; tumor self-seeded cells; invasion; photoconvertible tagging; CP: Cancer; cell population; liver cancer; TM4SF1
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114512

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. [Display omitted] •A mouse model of tumor self-seeding is developed using photoconvertible tagging•TSC is a subpopulation of primary tumor cells with enhanced invasion and survival•TM4SF1 is a key regulator of TSCs, promoting cancer cell migration, invasion, and survival•The potential TSC population with a metastatic profile is identified in patient tumors Tumor self-seeding is a process of circulating tumor cells recolonizing the primary tumor. Yang et al. develop a mouse model that recapitulates the spontaneous tumor self-seeding process and identifies tumor self-seeded cells (TSCs) highly expressing TM4SF1 with enhanced invasiveness and survival, providing cell targets with diagnostic, prognostic, or therapeutic potential.