Cancer metastasis is a physical process in which tumor cells break away from the primary tumor, enter, and then exit the blood or lymph vessels, and establish secondary tumors in distant organs. Current clinical studies report a higher risk of cancer metastasis for diabetics than non-diabetics. However, due to complex overlapping risk factors between diabetes and cancer, the mechanism underlying this correlation is largely unknown. Elevated lifetime blood sugar levels in diabetics are known to increase glycation of collagen, causing stiffening of the ECM and connective tissue. In this study, we explored the roles of glycation of 3D collagen matrices in tumor cell invasion and migration. Using time-lapse images, we quantitatively compared the motility behavior of malignant breast tumor cells (MDA-MB-231) and co-culture spheroids (1:1 ratio of MDA-MB-231 cells with normal epithelial MCF-10A cells) embedded in glycated and non-glycated collagen matrices of various concentrations. Experimental results demonstrated that glycation increased tumor invasion within collagen matrices. More specifically, the average speed of MDA-MB-231 cells was higher in glycated collagen gels than in non-glycated collagen gels for all three gel concentrations tested. Cell spreading characterized by its diffusion coefficient or the effective spheroid radii at various time points was significantly greater in glycated collagen than in non-glycated collagen at a concentration of 3.5 mg/mL. This enhancement was moderate and less evident at lower collagen concentrations of 1.0 and 2.0 mg/mL. These results suggest a possible biomechanical link that relates to the high blood sugar level in diabetic patients and the cancer metastatic outcome.

中文翻译：

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胶原基质的糖化促进乳腺肿瘤细胞侵袭。


癌症转移是肿瘤细胞脱离原发肿瘤，进入然后离开血管或淋巴管，在远处器官形成继发肿瘤的物理过程。目前的临床研究表明，糖尿病患者的癌症转移风险高于非糖尿病患者。然而，由于糖尿病和癌症之间复杂的重叠危险因素，这种相关性的机制在很大程度上尚不清楚。众所周知，糖尿病患者终生血糖水平升高会增加胶原蛋白的糖化，导致 ECM 和结缔组织僵硬。在这项研究中，我们探讨了 3D 胶原基质糖化在肿瘤细胞侵袭和迁移中的作用。使用延时图像，我们定量比较了恶性乳腺肿瘤细胞 (MDA-MB-231) 和共培养球体（MDA-MB-231 细胞与正常上皮 MCF-10A 细胞比例为 1:1）的运动行为存在于不同浓度的糖化和非糖化胶原蛋白基质中。实验结果表明，糖化增加了胶原基质内的肿瘤侵袭。更具体地说，对于所有测试的三种凝胶浓度，糖化胶原凝胶中的 MDA-MB-231 细胞的平均速度高于非糖化胶原凝胶中的平均速度。在浓度为 3.5 mg/mL 时，糖化胶原中以不同时间点的扩散系数或有效球体半径表征的细胞扩散明显大于非糖化胶原。这种增强作用是中等的，并且在胶原蛋白浓度较低（1.0 和 2.0 mg/mL）时不太明显。这些结果表明，糖尿病患者的高血糖水平和癌症转移结果可能存在生物力学联系。