Viscoelastic properties of human pancreatic tumors and in vitro constructs to mimic mechanical properties.
Viscoelastic properties of human pancreatic tumors and in vitro constructs to mimic mechanical properties.
复制标题
DOI：
10.1016/j.actbio.2017.11.037
复制
发表时间：
2018-03
影响因子：
9.7
通讯作者：
Simmons CS
中科院分区：
文献类型：
--
作者：
Rubiano A;Delitto D;Han S;Gerber M;Galitz C;Trevino J;Thomas RM;Hughes SJ;Simmons CS
胰腺导管腺癌（PDAC）几乎是普遍致命的，这在很大程度上是由于肿瘤相关基质（TAS）细胞产生的保护性纤维化屏障。这种屏障被认为可以促进癌细胞的存活，并阻碍了开发有效疗法的尝试。我们提出了一个三维体外系统，复制了PDAC微环境的机械特性，代表了理解疾病生物学的宝贵工具。中尺度压痕量化的粘弹性指标切除的恶性肿瘤，发炎的慢性胰腺炎地区，和组织学正常组织。胰腺炎（2.15 ± 0.41 kPa，平均值±标准差）和肿瘤（5.46 ± 3.18 kPa）的稳态模量（SSM）均高于正常组织（1.06 ± 0.25 kPa; p < 0.005）。胰腺炎组织的平均粘度（63.2 ± 26.7kPa·s）明显低于正常组织（252 ± 134 kPa·s）和肿瘤组织（349 ± 222 kPa·s）（P < 0.005）。为了模拟这种重塑行为，从人PDAC肿瘤中分离PDAC和TAS细胞。来自PDAC细胞的条件培养基用于培养TAS包埋的胶原水凝胶。7天后，对照培养基中的TAS包埋的凝胶达到接近正常胰腺的SSM（1.45 ± 0.12 kPa），而用条件培养基维持的凝胶达到与肿瘤一致的较高SSM（3.38 ± 0.146 kPa）。综上所述，我们已经证明了一种体外系统，重现了体内PDAC肿瘤的硬化。此外，我们对粘弹性的量化表明，结合粘度的弹性成像算法可能能够更准确地区分胰腺癌和胰腺炎。
Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large part due to a protective fibrotic barrier generated by tumor-associated stromal (TAS) cells. This barrier is thought to promote cancer cell survival and confounds attempts to develop effective therapies. We present a 3D in vitro system that replicates the mechanical properties of the PDAC microenvironment, representing an invaluable tool for understanding the biology of the disease. Mesoscale indentation quantified viscoelastic metrics of resected malignant tumors, inflamed chronic pancreatitis regions, and histologically normal tissue. Both pancreatitis (2.15 ± 0.41 kPa, Mean ± SD) and tumors (5.46 ± 3.18 kPa) exhibit higher Steady-State Modulus (SSM) than normal tissue (1.06 ± 0.25 kPa; p < 0.005). The average viscosity of pancreatitis samples (63.2 ± 26.7 kPa·s) is significantly lower than that of both normal tissue (252 ± 134 kPa·s) and tumors (349 ± 222 kPa·s; p < 0.005). To mimic this remodeling behavior, PDAC and TAS cells were isolated from human PDAC tumors. Conditioned media from PDAC cells was used to culture TAS-embedded collagen hydrogels. After 7 days, TAS-embedded gels in control medium reached SSM (1.45 ± 0.12 kPa) near normal pancreas, while gels maintained with conditioned medium achieved higher SSM (3.38 ± 0.146 kPa) consistent with tumors. Taken together, we have demonstrated an in vitro system that recapitulates in vivo stiffening of PDAC tumors. In addition, our quantification of viscoelastic properties suggests that elastography algorithms incorporating viscosity may be able to more accurately distinguish between pancreatic cancer and pancreatitis.
登录
查看更多内容
影响因子：
3.8
作者：
Bhana, Bashir;Iyer, Rohin K.;Radisic, Milica
通讯作者：
Radisic, Milica
影响因子：
3.7
作者：
Baker EL;Srivastava J;Yu D;Bonnecaze RT;Zaman MH
通讯作者：
Zaman MH
影响因子：
3.4
作者：
Baker, Erin L.;Lu, Jing;Zaman, Muhammad H.
通讯作者：
Zaman, Muhammad H.
影响因子：
8
作者：
Baker, A-M;Bird, D.;Erler, J. T.
通讯作者：
Erler, J. T.
影响因子：
4.8
作者：
Barcus, Craig E.;Keely, Patricia J.;Schuler, Linda A.
通讯作者：
Schuler, Linda A.