2. Academic Validation
  3. Laeverin is Cell-Surface Target for Liquid-Phase Metastasizing Cancer Cells

Laeverin is Cell-Surface Target for Liquid-Phase Metastasizing Cancer Cells

  • Adv Sci (Weinh). 2025 Sep 29:e11349. doi: 10.1002/advs.202511349.
Haruki Kasama 1,  Yuya Sakai 1,  Kyosuke Kagami 1,  Takashi Iizuka 1,  Tatsuhito Kanda 1,  Takuma Suzuki 1,  Kayo Kayahashi 1,  Masanori Ono 2,  Tomoko Fujiwara 3,  Shintaro Yagi 4,  Noriyuki Inaki 5,  Isao Matsumoto 6,  Rena Yamazaki 1,  Kaoru Abiko 1,  Noriomi Matsumura 7,  Akira Hattori 8,  Takiko Daikoku 9,  Hiroshi Fujiwara 1 10 11
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan.
  • 2 Department of Obstetrics and Gynecology, Tokyo Medical University, Nishi-Shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
  • 3 Department of Human Life Environments, Kyoto Notre Dame University, Kyoto, 606‑0847, Japan.
  • 4 Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kanazawa University Hospital, Kanazawa, 920‑8641, Japan.
  • 5 Department of Gastrointestinal Surgery, Kanazawa University, Kanazawa, 920-8641, Japan.
  • 6 Department of Thoracic Surgery, Kanazawa University Hospital, Kanazawa, 920-8641, Japan.
  • 7 Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka, 589‑8511, Japan.
  • 8 Department of System Chemotherapy and Molecular Sciences, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, 606-8501, Japan.
  • 9 Division of Animal Disease Model, Research Center for Experimental Modeling of Human Disease, Kanazawa University, Kanazawa, Ishikawa, 920-8640, Japan.
  • 10 Ochi Yume Clinic Nagoya, Nagoya, 460-0002, Japan.
  • 11 School of Veterinary Medicine, Azabu University, Sagamihara, 252-5201, Japan.
PMID: 41024351 DOI: 10.1002/advs.202511349
Abstract

Laeverin (LVRN) is a cell-surface immunoregulatory factor that is specifically expressed in embryo-derived extravillous trophoblast, which invades maternal spiral arteries without immune rejection during human placentation. Here, it is found that various epithelial Cancer cell lines upregulated LVRN expression in association with the expression of POU5F1 after spheroid formation under floating conditions. Immunohistochemically, LVRN expression is detected in the lesions of vascular, lymphatic, and peritoneal invasion of ovarian, cervical, endometrial, breast, and lung cancers. LVRN-positive circulating tumor cells are also identified in the blood of uterine cervical and endometrial cancers, showing that LVRN expression is induced in Cancer cells in the distant metastatic phase. Monomethylauristatin E-conjugated anti-LVRN antibody induced cell death in ovarian cancer-derived cell lines in the liquid phase in vitro and inhibited their peritoneal dissemination in nude mice in vivo. These findings indicate that LVRN is a unique and promising cell-surface target molecule for liquid-phase metastasizing Cancer cells.

Keywords

Oct4; antigen‐drug conjugate; cancer stem cell; distant metastasis; laeverin; liquid phase; spheroid.

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