AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025010560
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ORIGINAL RESEARCH ARTICLE

Secreted phosphoprotein 1 promotes ovarian cancer metastasis by regulating the function of cancer-associated fibroblasts

Xuerou Wang1 ,  Longyang Li1 ,  Jinglin Li2 ,  Wencao Tan1 ,  Xinyu Wang1 ,  Wan Fu1 ,  Linlin Li3 ,  Ya Xie1*
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1 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
2 Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
3 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
EJMO, 025010560 https://doi.org/10.36922/EJMO025010560
Received: 31 December 2025 | Revised: 1 April 2026 | Accepted: 9 April 2026 | Published online: 20 May 2026
(This article belongs to the Special Issue Tumor Immune Microenvironment and Intervention Strategies)
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Ovarian cancer is a leading cause of cancer-related mortality among females, characterized by its aggressive behavior and metastatic potential. Secreted phosphoprotein 1 (SPP1) has been implicated in various malignancies; however, its specific role in ovarian cancer and its effects on cancer-associated fibroblasts (CAFs) remain poorly understood.

Objectives: To analyze the expression level of SPP1 in ovarian cancer and its correlation with patients’ prognostic survival, and to investigate the specific effects and potential molecular mechanisms of SPP1 on CAFs through transcriptome sequencing and in vitro and in vivo assays.

Methods: We assessed SPP1 expression in high-grade serous ovarian cancer (HGSOC) tissues and its correlation with patient prognosis using Kaplan–Meier survival analysis and immunohistochemistry. CAFs and normal fibroblasts were isolated for further analysis.

Results: Co-culture experiments using mouse ovarian cancer cells and mouse fibroblasts (NIH/3T3) demonstrated that SPP1 enhances CAF migration and invasion. RNA sequencing revealed that SPP1 promotes the secretion of multiple cytokines from CAFs, including interleukin-6 and C-X-C motif chemokine ligand 1. Western blot analysis demonstrated that SPP1 treatment activates the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in CAFs. In vivo experiments using a mouse peritoneal metastasis model with co-cultured mouse ovarian cancer cells and mouse fibroblasts demonstrated that SPP1 knockdown significantly reduced ovarian cancer metastatic foci.

Conclusions: Our findings suggest that high SPP1 expression correlates with poor prognosis in patients with ovarian cancer and that SPP1 facilitates malignant progression by enhancing cytokine secretion in CAFs through the PI3K/AKT pathway, highlighting SPP1 as an attractive target for HGSOC therapy.

Keywords
High-grade serous ovarian cancer
Phosphoinositide 3-kinase/protein kinase B pathway
Tumor microenvironment
C-X-C motif chemokine ligand 1
Interleukin-6
Cancer-associated fibroblasts
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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