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<p>Perineural invasion (PNI) is frequent in pancreatic ductal adenocarcinoma (PDAC) and contributes to poor prognosis, yet stromal–neural mechanisms remain unclear. We developed a vertical multi-co-culture model incorporating human PDAC cells, neonatal mouse dorsal root ganglion (DRG) neurons, and human pancreatic stellate cells (PSCs). Migration assays demonstrated markedly greater PDAC cell migration in DRG + PSC than either condition alone. Proteomic profiling of conditioned media identified Secreted Protein Acidic and Rich in Cysteine (SPARC) as a highly enriched factor in the DRG + PSC condition. Public transcriptomic datasets (TCGA, GTEx, scRNA-seq) confirmed SPARC upregulation in PDAC, with predominant expression in fibroblasts and association with poor survival. Immunohistochemistry of 81 resected PDAC specimens in Hamamatsu University School of Medicine revealed stromal-rich SPARC expression significantly correlated with PNI-positive status. Collectively, these findings indicate that stromal SPARC is associated with PNI-related aggressiveness in PDAC. SPARC may serve as a biomarker of unfavorable prognosis and as a candidate stromal factor warranting future functional validation within the tumor-nerve-stromal axis.</p>

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SPARC is associated with tumor nerve stroma interactions and perineural invasion in pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月11日

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  • Satoru Furuhashi,
  • Ryuta Muraki,
  • Yoshifumi Morita,
  • Daiki Nishiwaki,
  • Akio Matsumoto,
  • Yuji Shimizu,
  • Tomohiro Murakami,
  • Makoto Takeda,
  • Hirotoshi Kikuchi,
  • Yoshihiro Hiramatsu,
  • Tomoaki Kahyo,
  • Mitsutoshi Setou,
  • Hiroya Takeuchi

摘要

Perineural invasion (PNI) is frequent in pancreatic ductal adenocarcinoma (PDAC) and contributes to poor prognosis, yet stromal–neural mechanisms remain unclear. We developed a vertical multi-co-culture model incorporating human PDAC cells, neonatal mouse dorsal root ganglion (DRG) neurons, and human pancreatic stellate cells (PSCs). Migration assays demonstrated markedly greater PDAC cell migration in DRG + PSC than either condition alone. Proteomic profiling of conditioned media identified Secreted Protein Acidic and Rich in Cysteine (SPARC) as a highly enriched factor in the DRG + PSC condition. Public transcriptomic datasets (TCGA, GTEx, scRNA-seq) confirmed SPARC upregulation in PDAC, with predominant expression in fibroblasts and association with poor survival. Immunohistochemistry of 81 resected PDAC specimens in Hamamatsu University School of Medicine revealed stromal-rich SPARC expression significantly correlated with PNI-positive status. Collectively, these findings indicate that stromal SPARC is associated with PNI-related aggressiveness in PDAC. SPARC may serve as a biomarker of unfavorable prognosis and as a candidate stromal factor warranting future functional validation within the tumor-nerve-stromal axis.