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<p>Lung cancer leads to a series of physiological abnormalities. The remodeling of extracellular matrix (especially elastin and collagen fibers) has been drawing increasing attention as it is suggested to be a hallmark of tumorigenesis. However, the interaction between these crucial matrix components, together with their relationship to mechanical changes, remains poorly understood. Here, we develop a quantitative multiphoton microscopy system to elucidate the relationship between tissue stiffening and elastin-collagen interplay in lung cancer. Based on label-free images of both fibers, we establish a metric termed resemblance metric (RM) to characterize their interaction by quantifying the similarity of their morpho-structural distributions. Specifically, RM is found to increase with lung tumorigenesis, and exhibits superior sensitivity in identifying human lung cancer through ex vivo quantitative imaging. Nanoindentation results suggest a strong correlation between tissue stiffness and inter-channel interaction, notably greater than that between stiffness and any individual morpho-structural feature of either fiber type. Finally, the translational potential of RM-based imaging is demonstrated through tumor boundary identification via in vivo imaging within a mouse model harboring human lung cancer.</p>

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Interpreting tissue stiffening with lung tumorigenesis by imaging architectural resembling of extracellular matrix components

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月8日

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  • Chuncheng Wang,
  • Shuhao Qian,
  • Wenyue Li,
  • Lingxi Zhou,
  • Lingmei Chen,
  • Jia Meng,
  • Rushan Jiang,
  • Bo Niu,
  • Ke Sun,
  • Zhihua Ding,
  • Xiaozhao Wang,
  • Shuangmu Zhuo,
  • Zhiyi Liu

摘要

Lung cancer leads to a series of physiological abnormalities. The remodeling of extracellular matrix (especially elastin and collagen fibers) has been drawing increasing attention as it is suggested to be a hallmark of tumorigenesis. However, the interaction between these crucial matrix components, together with their relationship to mechanical changes, remains poorly understood. Here, we develop a quantitative multiphoton microscopy system to elucidate the relationship between tissue stiffening and elastin-collagen interplay in lung cancer. Based on label-free images of both fibers, we establish a metric termed resemblance metric (RM) to characterize their interaction by quantifying the similarity of their morpho-structural distributions. Specifically, RM is found to increase with lung tumorigenesis, and exhibits superior sensitivity in identifying human lung cancer through ex vivo quantitative imaging. Nanoindentation results suggest a strong correlation between tissue stiffness and inter-channel interaction, notably greater than that between stiffness and any individual morpho-structural feature of either fiber type. Finally, the translational potential of RM-based imaging is demonstrated through tumor boundary identification via in vivo imaging within a mouse model harboring human lung cancer.