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Tumour cell-derived serglycin promotes IL-8 secretion of CAFs in gastric cancer.
Li, Xiang; Xie, Guiping; Chen, Jia; Wang, Yaohui; Zhai, Jing; Shen, Lizong.
Affiliation
  • Li X; Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
  • Xie G; Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
  • Chen J; Department of General Surgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China.
  • Wang Y; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211166, China.
  • Zhai J; Department of General Surgery, Northern Jiangsu People's Hospital, Yangzhou, 225001, China.
  • Shen L; Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
Br J Cancer ; 131(2): 271-282, 2024 Jul.
Article de En | MEDLINE | ID: mdl-38862740
ABSTRACT

BACKGROUND:

Cancer-associated fibroblasts (CAFs)-derived IL-8 plays important roles in chemoresistance, immunosuppression, and lymph node metastasis of gastric cancer. However, the mechanisms underlying IL-8 production in CAFs remains unclear.

METHODS:

DNA pulldown assay was performed to identify the transcription factors responsible for IL-8 expression in CAFs, which was further verified using CHIP-qPCR and DNA agarose gel electrophoresis assays. The cellular localisation of IL-8 was analysed using multiplex immunofluorescence (MxIF).

RESULTS:

MxIF demonstrated that IL-8 was mainly produced by CAFs in gastric cancer. Lysine[K]-specific demethylase 5B (KDM5B) was identified as an IL-8 transcription factor in CAFs, and the binding of KDM5B to phosphorylated RB1 limited the transcriptional regulation of IL-8 in gastric cancer cells. Serglycin (SRGN) secreted by tumour cells activated the CD44/c-Myc pathway to upregulate KDM5B expression, thereby promoting IL-8 production in CAFs. Furthermore, tumour-associated neutrophils (TANs)-derived regenerating family member 4 (REG4) upregulates SRGN expression by activating cAMP-responsive element binding protein 1 (CREB1) in gastric cancer cells. Thus, the SRGN-IL-8-TANs-SRGN loop, which facilitates tumour progression, has been explored in gastric cancer.

CONCLUSIONS:

This study revealed the mechanisms of the preferential production of IL-8 by CAFs in gastric cancer, and paves the way for potential new therapeutic strategies for gastric cancer.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Protéoglycanes / Tumeurs de l'estomac / Interleukine-8 / Protéines du transport vésiculaire / Fibroblastes associés au cancer Limites: Animals / Humans / Male Langue: En Journal: Br J Cancer Année: 2024 Type de document: Article Pays d'affiliation: Chine

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Protéoglycanes / Tumeurs de l'estomac / Interleukine-8 / Protéines du transport vésiculaire / Fibroblastes associés au cancer Limites: Animals / Humans / Male Langue: En Journal: Br J Cancer Année: 2024 Type de document: Article Pays d'affiliation: Chine