{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:18:58Z","timestamp":1787894338172,"version":"build-2784847793"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018925","name":"Health Commission of Henan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3389\/fonc.2026.1902341","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:34:32Z","timestamp":1787891672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["VCAN is upregulated in the cervical cancer stroma and modulates macrophage polarization"],"prefix":"10.3389","volume":"16","author":[{"given":"Shijia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongguo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University","place":["Zhengzhou, 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