Macroscopic stiffness of breast tumors predicts metastasis.

Macroscopic stiffness of breast tumors predicts metastasis.
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DOI:
10.1038/srep05512
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发表时间:
2014-07-01
期刊:
影响因子:
4.6
通讯作者:
Luker GD
Luker GD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fenner J;Stacer AC;Winterroth F;Johnson TD;Luker KE;Luker GD

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肿瘤的机械性质与正常细胞和组织有很大不同。硬度或弹性的变化调节癌细胞的促转移行为,但其作用主要在分离的细胞或体外细胞培养系统中被记录。为了将肿瘤的相对硬度与癌症进展直接联系起来,我们将转移性乳腺癌的小鼠模型与新鲜切除的完整肿瘤的体积模量的离体测量相结合。我们发现切除肿瘤的体积模量与随后的局部复发和转移之间存在高度的负相关性。与肿瘤相对坚硬的小鼠相比,更顺从的肿瘤与更频繁、更大的局部复发和更广泛的转移有关。我们发现切除肿瘤的胶原含量与体积弹性模量值相关。这些数据证实,肿瘤硬度的相对差异与肿瘤进展和转移相对应,支持进一步测试和开发肿瘤顺应性作为乳腺癌的预后生物标志物。
Mechanical properties of tumors differ substantially from normal cells and tissues. Changes in stiffness or elasticity regulate pro-metastatic behaviors of cancer cells, but effects have been documented predominantly in isolated cells or in vitro cell culture systems. To directly link relative stiffness of tumors to cancer progression, we combined a mouse model of metastatic breast cancer with ex vivo measurements of bulk moduli of freshly excised, intact tumors. We found a high, inverse correlation between bulk modulus of resected tumors and subsequent local recurrence and metastasis. More compliant tumors were associated with more frequent, larger local recurrences and more extensive metastases than mice with relatively stiff tumors. We found that collagen content of resected tumors correlated with bulk modulus values. These data establish that relative differences in tumor stiffness correspond with tumor progression and metastasis, supporting further testing and development of tumor compliance as a prognostic biomarker in breast cancer.
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