2. Academic Validation
  3. SPP1 represents a therapeutic target that promotes the progression of oesophageal squamous cell carcinoma by driving M2 macrophage infiltration

SPP1 represents a therapeutic target that promotes the progression of oesophageal squamous cell carcinoma by driving M2 macrophage infiltration

  • Br J Cancer. 2024 Apr 10. doi: 10.1038/s41416-024-02683-x.
Chen Wang 1 2,  Yutong Li 1 3 4,  Linhong Wang 1 3 4,  Yu Han 5,  Xiaohui Gao 1 3 4,  Tiandong Li 6,  Man Liu 7,  Liping Dai 1 3 4,  Renle Du 8 9 10 11
Affiliations

Affiliations

  • 1 Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 2 Department of Nuclear Medicine, Xinxiang Central Hospital, Xinxiang, 453002, Henan, China.
  • 3 Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 4 Henan Key Laboratory for Pharmacology of Liver Diseases, Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 5 Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 6 College of Public Health, Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 7 Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Zhengzhou, 450000, Henan, China.
  • 8 Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected].
  • 9 Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected].
  • 10 Henan Key Laboratory for Pharmacology of Liver Diseases, Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected].
  • 11 College of Public Health, Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected].
PMID: 38600327 DOI: 10.1038/s41416-024-02683-x
Abstract

Background: Tumour-associated macrophages (TAMs) are an important component of the tumour microenvironment (TME). However, the crosstalk between oesophageal squamous cell carcinoma (ESCC) cells and TAMs remains largely unexplored.

Methods: Clinical samples and the TCGA database were used to evaluate the relevance of SPP1 and TAM infiltration in ESCC. Mouse models were constructed to investigate the roles of macrophages educated by SPP1 in ESCC. Macrophage phenotypes were determined using qRT‒PCR and immunohistochemical staining. RNA sequencing was performed to elucidate the mechanism.

Results: Increasing expression of SPP1 correlated with M2-like TAM accumulation in ESCC, and they both predicted poor prognosis in the ESCC cohort. Knockdown of SPP1 significantly inhibited the infiltration of M2 TAMs in xenograft tumours. In vivo mouse model experiments showed that SPP1-mediated education of macrophages plays an essential role in the progression of ESCC. Mechanistically, SPP1 recruited macrophages and promoted M2 polarisation via CD44/PI3K/Akt signalling activation and then induced VEGFA and IL6 secretion to sustain ESCC progression. Finally, blockade of SPP1 with RNA aptamer significantly inhibited tumour growth and M2 TAM infiltration in xenograft mouse models.

Conclusions: This study highlights SPP1-mediated crosstalk between ESCC cells and TAMs in ESCC. SPP1 could serve as a potential target in ESCC therapy.

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