Mechanical remodeling of stromal collagen, such as reorientation and deformation of collagen matrix, generated by invading cancer cells, plays an important role in the progression of cancer invasion and metastasis. In this study, we applied time-lapse microscopy in conjunction with particle displacement mapping to analyze time-dependent contraction and expansion deformations of collagen surrounding individual spheroids of head and neck squamous cell carcinoma cells (HNSCC), OECM-1 & SAS, as the cancer cells detached from the spheroid and invaded into the surrounding 3D collagen matrix. Our results revealed that highly-invasive HNSCC spheroids, stimulated by epidermal growth factor (EGF), generated a strong contraction deformation of the surrounding collagen in the very early stage, and aligned the collagen fibers radially with respect to the center of the spheroid. This initial collagen contraction deformation generated by the HNSCC spheroid bears a strong positive correlation with the overall extent of subsequent cancer cells invasion; hence, it may serve as an early indicator of the invasion capability of the HNSCC spheroids. STATEMENT OF SIGNIFICANCE: Mechanical remodeling of extracellular matrix (ECM) generated by cancer cells plays an important role in the progression of cancer invasion and metastasis. We observed that the extent of initial contraction deformation of collagen surrounding a head and neck squamous cell carcinoma cell (HNSCC) spheroid played an indispensable role in early stage to promote cancer cells invasion into the surrounding ECM. Our results revealed that more invasive HNSCC spheroids generated a larger extent of initial collagen contraction to align the surrounding collagen and to promote cancer cells invasion. This initial collagen contraction deformation generated by the HNSCC spheroids bears a strong positive correlation with the overall extent of cancer cells invasion; hence, it may serve as an early indicator of the invasion capability of the HNSCC spheroids.

中文翻译：

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头颈部鳞状细胞癌球体周围胶原蛋白的早期机械重塑与其侵袭能力密切相关。

入侵癌细胞产生的基质胶原的机械重塑，例如胶原基质的重新定向和变形，在癌症侵袭和转移的进程中起着重要作用。在这项研究中，我们将延时显微镜与颗粒位移映射结合使用，分析了头颈部鳞状细胞癌细胞（HNSCC），OECM-1和SAS单个球体周围的胶原蛋白随时间变化的收缩和膨胀变形。癌细胞从球体上脱落，并侵入周围的3D胶原蛋白基质中。我们的研究结果表明，受表皮生长因子（EGF）刺激的高侵害性HNSCC球体在非​​常早期就产生了周围胶原蛋白的强烈收缩变形，并使胶原纤维相对于球体的中心呈放射状排列。HNSCC球体产生的这种最初的胶原蛋白收缩变形与随后的癌细胞侵袭的总体程度具有很强的正相关性。因此，它可以作为HNSCC球体侵袭能力的早期指标。意义声明：癌细胞产生的细胞外基质（ECM）的机械重塑在癌症侵袭和转移的进程中起着重要作用。我们观察到头颈部鳞状细胞癌细胞（HNSCC）球体周围的胶原蛋白的初始收缩变形程度在早期阶段起着促进癌细胞侵入周围ECM的必不可少的作用。我们的研究结果表明，更具侵入性的HNSCC球体会产生较大程度的初始胶原蛋白收缩，以对齐周围的胶原蛋白并促进癌细胞的侵袭。HNSCC球体产生的这种最初的胶原蛋白收缩变形与癌细胞侵袭的总体范围具有很强的正相关性。因此，它可以作为HNSCC球体侵袭能力的早期指标。