Identification and characterization of TM4SF1+ tumor self-seeded cells
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
Affiliations
Haotian Yang
Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; Gallipoli Medical Research, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia
Haolu Wang
Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; Gallipoli Medical Research, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia
Yaowu He
Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Yang Yang
Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia
Erik W. Thompson
School of Biomedical Sciences, Queensland University of Technology and Translational Research Institute, Brisbane, QLD 4000, Australia
Di Xia
Genome Innovation Hub, The University of Queensland, Brisbane, QLD 4072, Australia
Leslie J. Burke
Gallipoli Medical Research, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia
Lu Cao
Gallipoli Medical Research, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia
John D. Hooper
Mater Research Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Michael S. Roberts
Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia
Darrell H.G. Crawford
Gallipoli Medical Research, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia; Faculty of Medicine, The University of Queensland, Brisbane, QLD 4006, Australia
Xiaowen Liang
Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4102, Australia; Gallipoli Medical Research, Greenslopes Private Hospital, Brisbane, QLD 4120, Australia; Corresponding author
Summary: 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.
