Laeverin is Cell‐Surface Target for Liquid‐Phase Metastasizing Cancer Cells
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.
Authors
- Kayo Kayahashi
- Hiroshi Fujiwara (ORCID: https://orcid.org/0000-0003-3098-9406)
- Takuma Suzuki (ORCID: https://orcid.org/0009-0002-1098-9441)
- Kaoru Abiko (ORCID: https://orcid.org/0000-0001-9648-158X)
- Yuya Sakai (ORCID: https://orcid.org/0000-0002-6726-2609)
- Takashi Iizuka (ORCID: https://orcid.org/0000-0003-1885-6272)
- Tomoko Fujiwara (ORCID: https://orcid.org/0000-0002-3329-0361)
- Noriyuki Inaki (ORCID: https://orcid.org/0000-0002-4241-5015)
- Haruki Kasama
- Masanori Ono (ORCID: https://orcid.org/0000-0001-9249-6813)
- Tatsuhito Kanda
- Noriomi Matsumura (ORCID: https://orcid.org/0000-0002-4512-7975)
- Takiko Daikoku (ORCID: https://orcid.org/0000-0002-6280-8502)
- Akira Hattori (ORCID: https://orcid.org/0000-0001-5509-2326)
- Isao Matsumoto (ORCID: https://orcid.org/0000-0002-3335-1013)
- Shintaro Yagi
- Rena Yamazaki
- Kyosuke Kagami
Institutions
- Kanazawa University (JP)
- Tokyo Medical University (JP)
- Kanazawa Medical University (JP)
- Kyoto Pharmaceutical University (JP)
- Nagoya University Hospital (JP)
- Kanazawa University Hospital (JP)
- Kyoto Notre Dame University (JP)
- Azabu University (JP)
- Kindai University (JP)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1002/advs.202511349
- Primary Topic
- MicroRNA in disease regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00