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Prognostic Impact of Stromal Profiles Educated by Gastric Cancer

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Cancer-associated fibroblasts exhibit diversity and have several subtypes. The underlying relationship between the diversity of cancer-associated fibroblasts and their effect on gastric cancer progression remains unclear. In this study, mesenchymal stem cells were differentiated into cancer-associated fibroblasts with gastric cancer cell lines; clinical specimens were used to further investigate the impact of cancer-associated fibroblast diversity on cancer progression.

Methods

Nine gastric cancer cell lines (NUGC3, NUGC4, MKN7, MKN45, MKN74, FU97, OCUM1, NCI-N87, and KATOIII) were used to induce mesenchymal stem cell differentiation into cancer-associated fibroblasts. The cancer-associated fibroblasts were classified based on ACTA2 and PDPN expression. Cell function analysis was used to examine the impact of cancer-associated fibroblast subtypes on cancer cell phenotype. Tissue samples from 97gastric patients who underwent gastrectomy were used to examine the clinical significance of each subtype classified according to cancer-associated fibroblast expression.

Results

Co-culture of mesenchymal stem cells with nine gastric cancer cell lines revealed different subtypes of ACTA2 and PDPN expression in differentiated cancer-associated fibroblasts. Cancer-associated fibroblast subtypes with high ACTA2 plus PDPN expression levels significantly increased gastric cancer cell migration, invasion, and proliferation. The cancer-associated fibroblast subtype with ACTA2 plus PDPN expression was an independent prognostic factor along with lymph node metastasis for patients who had gastric cancer and were undergoing surgery.

Conclusions

Cancer-associated fibroblasts are educated by gastric cancer cells during the development of cancer-associated fibroblast diversity. Differentiated cancer-associated fibroblasts with distinct expression patterns could affect gastric cancer progression and enable prognostic stratification for gastric cancer.

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Acknowledgment

This work was partially supported by JSPS KAKENHI Grant Number 21K16442.

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Author notes

  1. Kazunori Takahashi, Katsutoshi Shoda and Koichi Takiguchi have contributed equally to this work.

Authors and Affiliations

  1. First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan

    Kazunori Takahashi MD, Katsutoshi Shoda MD, PhD, Koichi Takiguchi MD, PhD, Yudai Higuchi MD, Koichi Matsuoka MD, Takashi Nakayama MD, Ryo Saito MD, PhD, Suguru Maruyama MD, PhD, Yuki Nakata MD, PhD, Shinji Furuya MD, PhD, Kensuke Shiraishi MD, PhD, Hidenori Akaike MD, PhD, Yoshihiko Kawaguchi MD, PhD, Hidetake Amemiya MD, PhD, Hiromichi Kawaida MD, PhD & Daisuke Ichikawa MD, PhD

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All authors contributed to the final manuscript.

Corresponding author

Correspondence to Katsutoshi Shoda MD, PhD.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. All the patients provided written informed consent for surgery and the use of their clinical data, as required by the Institutional Review Board of the Yamanashi University (approved number 2567).

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Takahashi, K., Shoda, K., Takiguchi, K. et al. Prognostic Impact of Stromal Profiles Educated by Gastric Cancer. Ann Surg Oncol 31, 2309–2318 (2024). https://doi.org/10.1245/s10434-023-14522-z

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