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Probing the biophysical properties of primary breast tumor-derived fibroblasts

机译:探索原发性乳腺肿瘤衍生的成纤维细胞的生物物理特性

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摘要

As cancer progresses, cells must adapt to a new and stiffer environment, which can ultimately alter how normal cells within the tumor behave. In turn, these cells are known to further aid tumor progression. Therefore, there is potentially a unique avenue to better understand metastatic potential through single-cell biophysical assays performed on patient-derived cells. Here, we perform biophysical characterization of primary human fibroblastic cells obtained from mammary carcinoma and normal contralateral tissue. Through a series of tissue dissociation, differential centrifugation and trypsinization steps, we isolate an adherent fibroblastic population viable for biomechanical testing. 2D TFM and 3D migration measurements in a collagen matrix show that fibroblasts obtained from patient tumors generate more traction forces and display improved migration potential than their counterparts from normal tissue. Moreover, through the use of an embedded spheroid model, we confirmed the extracellular matrix (ECM) remodeling behavior of primary cells isolated from carcinoma. Overall, correlating biophysical characterization of normal- and carcinoma-derived samples from individual patient along with patient outcome may become a powerful approach to further our comprehension of metastasis and ultimately design drug targets on a patient-specific basis.
机译:随着癌症的进展,细胞必须适应新的更硬的环境,这最终会改变肿瘤内正常细胞的行为。进而,已知这些细胞进一步帮助肿瘤进展。因此,潜在的独特途径可以通过对患者来源的细胞进行单细胞生物物理测定来更好地了解转移潜能。在这里,我们执行从乳腺癌和正常对侧组织获得的原代人成纤维细胞的生物物理表征。通过一系列的组织分离,离心分离和胰蛋白酶消化步骤,我们分离出了可行的生物力学测试粘附成纤维细胞群体。在胶原蛋白基质中进行的2D TFM和3D迁移测量表明,从患者肿瘤获得的成纤维细胞比正常组织的成纤维细胞产生更多的牵引力并显示出更高的迁移潜力。此外,通过使用嵌入式球体模型,我们证实了分离自癌的原代细胞的细胞外基质(ECM)重塑行为。总体而言,将来自各个患者的正常和癌症来源的样品的生物物理特征与患者的结果相关联,可能会成为一种强大的方法,有助于我们进一步了解转移情况,并最终根据患者的具体情况设计药物靶标。

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