2024年 新着論文 25 発生生物学分野から論文が発表されました

 

Tumor endothelial cell-derived Sfrp1 supports the maintenance of cancer stem cells via Wnt signaling

In Vitro Cell Dev Biol Anim. 2024 Apr 16. doi: 10.1007/s11626-024-00899-y. Online ahead of print.

Authors

Yumiko Hayashi  1   2 Masakazu Hashimoto  3 Katsuyoshi Takaoka  4 Tatsuya Takemoto  4 Nobuyuki Takakura  2   5   6   7 Hiroyasu Kidoya  8   9

Affiliations

  • 1 Department of Integrative Vascular Biology, Faculty of Medical Science, Fukui University, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan.
  • 2 Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • 3 Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
  • 4 Laboratory for Embryology, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.
  • 5 World Premier Institute Immunology Frontier Research Center, Integrated Frontier Research for Medical Science Division, Osaka University, Suita, Japan.
  • 6 Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Japan.
  • 7 Center for Infectious Disease Education and Research, Osaka University, Suita, Japan.
  • 8 Department of Integrative Vascular Biology, Faculty of Medical Science, Fukui University, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Yoshida, Fukui, 910-1193, Japan. kidoya@u-fukui.ac.jp.
  • 9 Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Japan. kidoya@u-fukui.ac.jp.

Abstract

Cancer stem cells (CSCs), which are critical targets for cancer therapy as they are involved in drug resistance to anticancer drugs, and metastasis, are maintained by angiocrine factors produced by particular niches that form within tumor tissue. Secreted frizzled-related protein 1 (Sfrp1) is an extracellular protein that modulates Wnt signaling. However, the cells that produce Sfrp1 in the tumor environment and its function remain unclear. We aimed to elucidate angiocrine factors related to CSC maintenance, focusing on Sfrp1. Although Sfrp1 is a Wnt pathway-related factor, its impact on tumor tissues remains unknown. We investigated the localization of Sfrp1 in tumors and found that it is expressed in some tumor vessels. Analysis of mice lacking Sfrp1 showed that tumor growth was suppressed in Sfrp1-deficient tumor tissues. Flow cytometry analysis indicated that CSCs were maintained in the early tumor growth phase in the Sfrp1 knockout (KO) mouse model of tumor-bearing cancer. However, tumor growth was inhibited in the late tumor growth phase because of the inability to maintain CSCs. Real-time PCR results from tumors of Sfrp1 KO mice showed that the expression of Wnt signaling target genes significantly decreased in the late stage of tumor growth. This suggests that Sfrp1, an angiocrine factor produced by the tumor vascular niche, is involved in Wnt signaling-mediated mechanisms in tumor tissues.

Keywords: Angiocrine factor; Cancer stem cell; Sfrp1; Tumor endothelial cell; Wnt signaling.