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<p>Pancreatic cancer is an aggressive disease with a dense fibrotic stroma and is often accompanied by chronic inflammation. Peritumoral inflammation is typically viewed as a reaction to nearby tumor growth. Here, we report that the inflamed pancreatic lobules are frequently invaded by tumor cells, forming a distinct, non-fibrotic tumor niche. Using a semi-supervised machine learning approach for annotations of clinical samples and multiplex protein profiling, we show that tumor cells at the invasion front are closely associated with acinar cells undergoing damage-induced changes, and with activated fibroblasts expressing markers of injury. The invaded lobules are linked to classical tumor phenotypes, in contrast to fibrotic areas where tumor cells display a more basal profile, highlighting microenvironment-dependent tumor subtype differences. In female mice, lobular invasion similarly aligns with the classical tumor phenotype. Together, our data reveal that pancreatic tumors colonize injured lobules, creating a unique niche that shapes tumor characteristics and contributes to disease biology.</p>

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An injury-associated lobular microniche is associated with the classical tumor cell phenotype in pancreatic cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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  • Sara Söderqvist,
  • Annika Viljamaa,
  • Natalie Geyer,
  • Anna-Lena Keller,
  • Kseniya Ruksha,
  • Carina Strell,
  • Neda Hekmati,
  • Alexandra Niculae,
  • Jennie Engstrand,
  • Ernesto Sparrelid,
  • Caroline Salmén,
  • Tânia D. F. Costa,
  • Miao Zhao,
  • Staffan Strömblad,
  • Argyro Zacharouli,
  • Poya Ghorbani,
  • Sara Harrizi,
  • Yousra Hamidi,
  • Olga Khorosjutina,
  • Stefina Milanova,
  • Bernhard Schmierer,
  • Béla Bozóky,
  • Carlos Fernández Moro,
  • Marco Gerling

摘要

Pancreatic cancer is an aggressive disease with a dense fibrotic stroma and is often accompanied by chronic inflammation. Peritumoral inflammation is typically viewed as a reaction to nearby tumor growth. Here, we report that the inflamed pancreatic lobules are frequently invaded by tumor cells, forming a distinct, non-fibrotic tumor niche. Using a semi-supervised machine learning approach for annotations of clinical samples and multiplex protein profiling, we show that tumor cells at the invasion front are closely associated with acinar cells undergoing damage-induced changes, and with activated fibroblasts expressing markers of injury. The invaded lobules are linked to classical tumor phenotypes, in contrast to fibrotic areas where tumor cells display a more basal profile, highlighting microenvironment-dependent tumor subtype differences. In female mice, lobular invasion similarly aligns with the classical tumor phenotype. Together, our data reveal that pancreatic tumors colonize injured lobules, creating a unique niche that shapes tumor characteristics and contributes to disease biology.