Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model.
Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model.
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DOI：
10.1039/c3ib00008g
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Davalos RV
中科院分区：
文献类型：
--
作者：
Salmanzadeh A;Elvington ES;Roberts PC;Schmelz EM;Davalos RV
目前，传统的癌症治疗方案通常依赖于高毒性的化疗药物或靶向癌基因，这些基因在肿瘤的不同细胞群体中可变地表达。这些挑战突显了对新的治疗策略的需求：1)无毒但至少能够部分地将疾病的侵袭性表型逆转为良性或生长非常缓慢的状态，以及2)独立于可变表达的生物标记物作用于细胞。使用一种称为无接触双向凝胶电泳(CDEP)的标记非依赖的快速微流控细胞操作策略，我们研究了两种具有潜在抗肿瘤特性的生物活性鞘氨醇代谢物-鞘氨醇(SO)和促肿瘤代谢物鞘氨醇-1-磷酸(S1P)的无毒浓度对小鼠卵巢表面上皮(MOSE)癌细胞早期和晚期内在电特性的影响。在此之前，我们证明了随着细胞从良性的早期发展到晚期的恶性，电学性质发生了变化。在这里，我们证明了SO治疗与晚期MOSE(MOSE-L)细胞的生物电学特征向类似于良性MOSE-E细胞的方向转变之间的关联。经SO处理后，MOSE-L细胞的比膜电容向MOSE-E细胞移动，由23.94±2.75降至16.46±0.62mF/m2，膜突起减少。相反，S1P并不逆转MOSE-L细胞的电学特性。这项工作首次表明，无毒剂量的SO处理与细胞电特性和表面粗糙度的变化相关。它还展示了CDEP作为一种新的、快速的技术用于药物疗效研究的潜力，并最终设计出更个性化的治疗方案。
Currently, conventional cancer treatment regimens often rely upon highly toxic chemotherapeutics or target oncogenes that are variably expressed within the heterogeneous cell population of tumors. These challenges highlight the need for novel treatment strategies that 1) are non-toxic yet able to at least partially reverse the aggressive phenotype of the disease to a benign or very slow-growing state, and 2) act on the cells independently of variably expressed biomarkers. Using a label-independent rapid microfluidic cell manipulation strategy known as contactless dielectrophoresis (cDEP), we investigated the effect of non-toxic concentrations of two bioactive sphingolipid metabolites, sphingosine (So), with potential anti-tumor properties, and sphingosine-1-phosphate (S1P), a tumor-promoting metabolite, on the intrinsic electrical properties of early and late stages of mouse ovarian surface epithelial (MOSE) cancer cells. Previously, we demonstrated that electrical properties change as cells progress from a benign early stage to late malignant stages. Here, we demonstrate an association between So treatment and a shift in the bioelectrical characteristics of late stage MOSE (MOSE-L) cells towards a profile similar to that of benign MOSE-E cells. Particularly, the specific membrane capacitance of MOSE-L cells shifted toward that of MOSE-E cells, decreasing from 23.94±2.75 to 16.46±0.62 mF/m2 after So treatment, associated with a decrease in membrane protrusions. In contrast, S1P did not reverse the electrical properties of MOSE-L cells. This work is the first to indicate that treatment with non-toxic doses of So correlates with changes in the electrical properties and surface roughness of cells. It also demonstrates the potential of cDEP to be used as a new, rapid technique for drug efficacy studies, and eventually designing more personalized treatment regimens.
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影响因子：
1.8
作者：
ARNOLD, WM;ZIMMERMANN, U
通讯作者：
ZIMMERMANN, U
DOI：
10.1073/pnas.92.3.860
发表时间：
1995-01-31
影响因子：
11.1
作者：
BECKER, FF;WANG, XB;GASCOYNE, PRC
通讯作者：
GASCOYNE, PRC
影响因子：
7.4
作者：
Khoshmanesh, Khashayar;Akagi, Jin;Wlodkowic, Donald
通讯作者：
Wlodkowic, Donald
影响因子：
3.9
作者：
Lemonnier, LA;Dillehay, DL;Schmelz, EM
通讯作者：
Schmelz, EM
影响因子：
4.4
作者：
Gascoyne, PRC;Wang, XB;Becker, FF
通讯作者：
Becker, FF