Date: Sept. 2, 2025

Publisher: Jinan University Integrated Media Center

Editor: Li Mei

A research team led by Professors Ye Wencai and Zhang Dongmei from the College of Pharmacy at Jinan University has achieved significant breakthroughs in the field of tumor pericyte research. Their findings have been successively published in the internationally renowned journals Gut and Nature Communications. The study provides an in-depth exploration of the critical role of pericytes in tumor hematogenous metastasis and identifies potential new therapeutic targets.

Distant metastasis is the primary cause of cancer-related mortality, with hematogenous spread being a major pathway. As gatekeepers of tumor blood vessels, pericytes regulate tumor cell dissemination by maintaining vascular homeostasis. However, the specific mechanisms by which pericytes contribute to metastasis have remained unclear.

In the first study, published in Gut, the team observed that clusters formed by circulating tumor cells (CTCs) and neutrophils accumulate along the inner walls of blood vessels at the primary tumor site. Using single-cell sequencing, the researchers identified a new subpopulation of pericytes characterized by high expression of nicotinamide N-methyltransferase (NNMT). Mechanistic studies revealed that NNMT promotes the formation of CTC-neutrophil clusters by secreting CXCL5, which activates the CXCR2 signaling axis, thereby enhancing liver metastasis in colorectal cancer. Based on these findings, the team successfully developed a NNMT-targeted inhibitor, Z-GP-NNMTi, which effectively disrupts cluster formation and suppresses metastasis.

In another study published in Nature Communications, the team focused on the hemodynamic processes regulated by pericytes. They discovered that pericytes with high expression of NKX2-3 inhibit calcium influx through the PDE1C/cAMP/PKA signaling axis, leading to tumor vasodilation, increased blood flow, and vascular leakage, thereby facilitating hematogenous metastasis in colorectal cancer. Suppressing NKX2-3 transcriptional activity—either through gene deletion of *Nkx2-3* or treatment with a TCF21 fragment peptide—induced vasoconstriction and significantly inhibited metastasis.

These findings systematically clarify the heterogeneity of pericytes and their core regulatory mechanisms in tumor metastasis. The research not only enhances the understanding of tumor biology but also opens new avenues for the development of anti-metastatic drugs targeting pericytes, demonstrating significant academic value and promising clinical translation prospects.

Full-text links:

https://gut.bmj.com/lookup/pmidlookup?view=long&pmid=40701795

https://www.nature.com/articles/s41467-025-62475-6