Secretory GFP reconstitution labeling of neighboring cells interrogates cell–cell interactions in metastatic niches

Misa Minegishi, Takahiro Kuchimaru, Kaori Nishikawa, Takayuki Isagawa, Satoshi Iwano, Kei Iida, Hiromasa Hara, Shizuka Miura, Marika Sato, Shigeaki Watanabe, Akifumi Shiomi, Yo Mabuchi, Hiroshi Hamana, Hiroyuki Kishi, Tatsuyuki Sato, Daigo Sawaki, Shigeru Sato, Yutaka Hanazono, Atsushi Suzuki, Takahide KohroTetsuya Kadonosono, Tomomi Shimogori, Atsushi Miyawaki, Norihiko Takeda, Hirofumi Shintaku, Shinae Kizaka-Kondoh, Satoshi Nishimura

Research output: Contribution to journalArticlepeer-review


Cancer cells inevitably interact with neighboring host tissue-resident cells during the process of metastatic colonization, establishing a metastatic niche to fuel their survival, growth, and invasion. However, the underlying mechanisms in the metastatic niche are yet to be fully elucidated owing to the lack of methodologies for comprehensively studying the mechanisms of cell–cell interactions in the niche. Here, we improve a split green fluorescent protein (GFP)-based genetically encoded system to develop secretory glycosylphosphatidylinositol-anchored reconstitution-activated proteins to highlight intercellular connections (sGRAPHIC) for efficient fluorescent labeling of tissue-resident cells that neighbor on and putatively interact with cancer cells in deep tissues. The sGRAPHIC system enables the isolation of metastatic niche-associated tissue-resident cells for their characterization using a single-cell RNA sequencing platform. We use this sGRAPHIC-leveraged transcriptomic platform to uncover gene expression patterns in metastatic niche-associated hepatocytes in a murine model of liver metastasis. Among the marker genes of metastatic niche-associated hepatocytes, we identify Lgals3, encoding galectin-3, as a potential pro-metastatic factor that accelerates metastatic growth and invasion.

Original languageEnglish
Article number8031
JournalNature communications
Issue number1
Publication statusPublished - 12-2023

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy


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