We provide an innovative, bioengineering, mechanobiology-based approach to rapidly (2-h) establish the in vivo metastatic likelihood of patient tumor-samples, where results are in direct agreement with clinical histopathology and patient outcomes. Cancer-related mortality is mostly due to local recurrence or to metastatic disease, thus early prediction of tumor-cell-fate may critically affect treatment protocols and survival rates. Metastasis and recurrence risks are currently predicted by lymph-node status, tumor size, histopathology and genetic testing, however, these are not infallible and results may require days/weeks. We have previously observed that subpopulations of invasive cancer-cells will rapidly (1–2 h) push into the surface of physiological-stiffness, synthetic polyacrylamide gels, reaching to cell-scale depths, while normal or noninvasive cells do not considerably indent gels. Here, we evaluate the mechanical invasiveness of established breast and pancreatic cell lines and of tumor-cells from fresh, suspected pancreatic cancer tumors. The mechanical invasiveness matches the in vitro metastatic potential in cell lines as determined with Boyden chamber assays. Moreover, the mechanical invasiveness directly agrees with the clinical histopathology in primary-site, pancreatic-tumors. Thus, the rapid, patient-specific, early prediction of metastatic likelihood, on the time-scale of initial resection/biopsy, can directly affect disease management and treatment protocols.

我们提供了一种创新的、生物工程的、基于机械生物学的方法来快速（2 小时）建立体内患者肿瘤样本的转移可能性，其结果与临床组织病理学和患者结果直接一致。癌症相关死亡率主要是由于局部复发或转移性疾病，因此对肿瘤细胞命运的早期预测可能会严重影响治疗方案和存活率。目前通过淋巴结状态、肿瘤大小、组织病理学和基因检测来预测转移和复发风险，然而，这些并不是绝对可靠的，结果可能需要数天/数周。我们之前已经观察到侵袭性癌细胞亚群将迅速（1-2 小时）推入生理硬度的合成聚丙烯酰胺凝胶的表面，达到细胞级深度，而正常或非侵袭性细胞不会显着缩进凝胶。这里，我们评估了已建立的乳腺和胰腺细胞系以及来自新鲜疑似胰腺癌肿瘤的肿瘤细胞的机械侵袭性。机械侵入性匹配用博伊登室测定法测定的细胞系的体外转移潜能。此外，机械侵入性与原发部位胰腺肿瘤的临床组织病理学直接一致。因此，在初始切除/活检的时间尺度上对转移可能性的快速、患者特异性、早期预测，可以直接影响疾病管理和治疗方案。