Identification of Galectin-7 as a crucial metastatic enhancer of squamous cell carcinoma associated with immunosuppression

Jianbo An, Yushi Nagaki, Satoru Motoyama, Yuta Kuze, Midori Hoshizaki, Kohei Kemuriyama, Tomokazu Yamaguchi, Takashi Ebihara, Yoshihiro Minamiya, Yutaka Suzuki, Yumiko Imai, Keiji Kuba

研究成果: ジャーナルへの寄稿学術誌査読

5 被引用数 (Scopus)

抄録

Metastasis predicts poor prognosis in cancer patients. It has been recognized that specific tumor microenvironment defines cancer cell metastasis, whereas the underlying mechanisms remain elusive. Here we show that Galectin-7 is a crucial mediator of metastasis associated with immunosuppression. In a syngeneic mouse squamous cell carcinoma (SCC) model of NR-S1M cells, we isolated metastasized NR-S1M cells from lymph nodes in tumor-bearing mice and established metastatic NR-S1M cells in in vitro culture. RNA-seq analysis revealed that interferon gene signature was markedly downregulated in metastatic NR-S1M cells compared with parental cells, and in vivo NR-S1M tumors heterogeneously developed focal immunosuppressive areas featured by deficiency of anti-tumor immune cells. Spatial transcriptome analysis (Visium) for the NR-S1M tumors revealed that various pro-metastatic genes were significantly upregulated in immunosuppressive areas when compared to immunocompetent areas. Notably, Galectin-7 was identified as a novel metastasis-driving factor. Galectin-7 expression was induced during tumorigenesis particularly in the microenvironment of immunosuppression, and extracellularly released at later stage of tumor progression. Deletion of Galectin-7 in NR-S1M cells significantly suppressed lymph node and lung metastasis without affecting primary tumor growth. Therefore, Galectin-7 is a crucial mediator of tumor metastasis of SCC, which is educated in the immune-suppressed tumor areas, and may be a potential target of cancer immunotherapy.

本文言語英語
ページ(範囲)5319-5330
ページ数12
ジャーナルOncogene
41
50
DOI
出版ステータス出版済み - 12月 9 2022

!!!All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 遺伝学
  • 癌研究

フィンガープリント

「Identification of Galectin-7 as a crucial metastatic enhancer of squamous cell carcinoma associated with immunosuppression」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル