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Research Article: VCAN is upregulated in the cervical cancer stroma and modulates macrophage polarization

Date Published: 2026-08-28

Abstract:
The extracellular matrix (ECM) is a major component of the tumor microenvironment (TME) and plays an important role in cervical cancer progression. Versican, encoded by the VCAN gene, is a member of the aggrecan/proteoglycan family and has been reported as a marker of poor prognosis in cervical cancer. However, the versican-producing cells in cervical cancer tissue are not clearly identified. To identify the versican-producing cells in cervical cancer tissue, single-cell RNA sequencing (scRNA-seq) data of cervical cancer tissue are re-analyzed, and we find that versican is highly expressed in monocytes and fibroblasts. Immunohistochemical staining of cervical cancer and adjacent normal tissues showed that versican was predominantly expressed in non-parenchymal cells. Multiplex immunofluorescence staining further identified versican-expressing macrophages in cervical cancer tissues. We subsequently collected peripheral blood mononuclear cells (PBMCs) from a patient with cervical cancer before and after radiotherapy and performed scRNA-seq to investigate the highly variable genes in PBMCs. Notably, VCAN was identified as a monocyte-enriched gene and showed relatively high expression in the patient’s circulating monocytes. We further investigated the effect of Versican core protein (VCAN-V3) on macrophages. The results suggest that VCAN-V3 predominantly suppresses M1-associated gene expression and induces a partial shift toward an M2-like transcriptional phenotype in RAW264.7 cells. In conclusion, our study demonstrates that stromal VCAN is upregulated in cervical cancer tissue. VCAN-V3 may influence the tumor microenvironment by modulating macrophage polarization-associated responses.

Introduction:
Cervical cancer is one of the most common malignancies among women worldwide ( 1 ). For early-stage and locally invasive cervical cancer, the treatment includes surgery and concurrent chemotherapy and radiation therapy ( 1 , 2 ). Concurrent chemoradiotherapy is the standard of care for most stages of locally advanced cervical cancer. However, more than half of patients who receive concurrent chemoradiotherapy will develop recurrent disease or distant metastasis ( 2 ). The extracellular matrix (ECM) is an important…

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