Prognostic Impact of Stromal Profiles Educated by Gastric Cancer

被引:0
作者
Takahashi, Kazunori [1 ]
Shoda, Katsutoshi [1 ]
Takiguchi, Koichi [1 ]
Higuchi, Yudai [1 ]
Matsuoka, Koichi [1 ]
Nakayama, Takashi [1 ]
Saito, Ryo [1 ]
Maruyama, Suguru [1 ]
Nakata, Yuki [1 ]
Furuya, Shinji [1 ]
Shiraishi, Kensuke [1 ]
Akaike, Hidenori [1 ]
Kawaguchi, Yoshihiko [1 ]
Amemiya, Hidetake [1 ]
Kawaida, Hiromichi [1 ]
Ichikawa, Daisuke [1 ]
机构
[1] Univ Yamanashi, Dept Surg 1, Fac Med, Chuo, Yamanashi, Japan
关键词
Cancer-associated fibroblast; Gastric cancer; Prognosis; Microenvironment; MESENCHYMAL STEM-CELLS; PODOPLANIN EXPRESSION; PLATELET-AGGREGATION; FIBROBLASTS; MYOFIBROBLASTS; ADENOCARCINOMA; IDENTIFICATION; PROGRESSION; CARCINOMA;
D O I
10.1245/s10434-024-14888-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页码:2309 / 2318
页数:10
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