Modulation of matrix elasticity with PEG hydrogels to study melanoma drug responsiveness.
Modulation of matrix elasticity with PEG hydrogels to study melanoma drug responsiveness.
复制标题
用 PEG 水凝胶调节基质弹性以研究黑色素瘤药物反应性。
DOI：
10.1016/j.biomaterials.2014.01.063
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发表时间：
2014
期刊：
影响因子：
14
通讯作者：
Anseth,KristiS
中科院分区：
文献类型：
--
作者：
Tokuda,EmiY;Leight,JenniferL;Anseth,KristiS
转移性黑色素瘤对药物治疗高度耐药，这种耐药的潜在机制仍不清楚。增加的组织硬度与肿瘤进展相关，但增加的组织硬度是否有助于黑色素瘤的治疗抗性尚不清楚。为了研究基质硬度对黑色素瘤细胞治疗响应性的影响，将PEG水凝胶用作细胞培养系统以精确改变基质弹性并研究黑色素瘤细胞对市售药理学抑制剂（PLX4032）的响应。拉伸模量在0.6和13.1 kPa（E）之间变化，并在源自放射状生长期（WM 35）和转移性黑素瘤（A375）的人细胞系上评价了PLX4032对代谢活性、细胞凋亡和增殖的影响。A375细胞被认为是刚度独立的，基质弹性没有改变细胞形态或凋亡与PLX4032治疗。然而，WM35细胞更依赖于基底模量，在顺应性基底上显示出增加的凋亡和较小的粘着斑。在PEG水凝胶上培养黑色素瘤细胞揭示了对PLX4032的阶段依赖性反应，如果严格在TCPS上培养，这些反应将被掩盖。这些发现证明了PEG水凝胶作为黑色素瘤体外培养平台的实用性，其用于研究黑色素瘤生物学和治疗反应性的分子机制。
Metastatic melanoma is highly resistant to drug treatment, and the underlying mechanisms of this resistance remain unclear. Increased tissue stiffness is correlated with tumor progression, but whether increased tissue stiffness contributes to treatment resistance in melanoma is not known. To investigate the effect of substrate stiffness on melanoma cell treatment responsiveness, PEG hydrogels were utilized as a cell culture system to precisely vary matrix elasticity and investigate melanoma cell responses to a commercially available pharmacological inhibitor (PLX4032). The tensile moduli were varied between 0.6 and 13.1 kPa (E) and the effects of PLX4032 on metabolic activity, apoptosis, and proliferation were evaluated on human cell lines derived from radial growth phase (WM35) and metastatic melanoma (A375). The A375 cells were found to be stiffness-independent; matrix elasticity did not alter cell morphology or apoptosis with PLX4032 treatment. The WM35 cells, however, were more dependent on substrate modulus, displaying increased apoptosis and smaller focal adhesions on compliant substrates. Culturing melanoma cells on PEG hydrogels revealed stage-dependent responses to PLX4032 that would have otherwise been masked if cultured strictly on TCPS. These findings demonstrate the utility of PEG hydrogels as a versatilein vitroculture platform with which to investigate the molecular mechanisms of melanoma biology and treatment responsiveness.
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影响因子：
11.2
作者：
S. Albelda;S. Mette;D. Elder;R. Stewart;L. Damjanovich;M. Herlyn;C. Buck
通讯作者：
S. Albelda;S. Mette;D. Elder;R. Stewart;L. Damjanovich;M. Herlyn;C. Buck
影响因子：
3.8
作者：
Tibbitt, Mark W.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
I期皮肤黑色素瘤的手术治疗。
影响因子：
11.8
作者：
A. Breslow
通讯作者：
A. Breslow
影响因子：
9.7
作者：
Gould, Sarah T.;Darling, Nicole J.;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
DOI：
--
发表时间：
2005
期刊：
影响因子：
--
作者：
S. Bryant;K. Anseth
通讯作者：
K. Anseth