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

研究成果: ジャーナルへの寄稿学術論文査読

2 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号8031
ジャーナルNature communications
14
1
DOI
出版ステータス出版済み - 12-2023

All Science Journal Classification (ASJC) codes

  • 化学一般
  • 生化学、遺伝学、分子生物学一般
  • 物理学および天文学一般

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