Purnell Marcy C
Department of Microbiology, Immunology and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN 38163, USA and The Loewenberg College of Nursing, University of Memphis, Memphis, TN 38152, USA.
Discov Med. 2017 Apr;23(127):259-267.
Mechanisms that regulate cancer cell metastasis are often intricately linked to mechanisms that control cell migration in wound repair. Hyaluronan Mediated Motility Receptor (HMMR) encodes a receptor for hyaluronan-mediated motility (RHAMM), a non-integral cell surface hyaluronan receptor and intracellular protein that promotes mitotic spindle formation and cell motility. RHAMM has been found to have increased expression in both cancers and wounds, and when cancers show increased RHAMM expression poor outcomes have occurred. Therefore, RHAMM has been shown to contribute to both natural healing mechanisms and cancer cell pathology. RHAMM is expressed in breast tissue and forms a polarity normalizing complex with BRCA1. Mutations of BRCA1 have been associated with a loss of apicobasal cell polarity along with a subsequent increased expression of RHAMM. Here we show how a human breast carcinoma cell line was maintained in media prepared with a dilute saline solution that had been exposed to a dielectrophoretic (DEP) electromagnetic field (EMF) generated by 3 amperes of direct current (dc) to a device housing an array of conductive rings. This Bio-electric Field Enhancement (BEFE) device has been available commercially for use in baths/footbaths since 1996 and consumers claim that it provides health benefits ranging from lowering blood pressure to faster wound healing. Our studies showed a significant inhibition of growth of human breast carcinoma MDA-MB-231 cells when they were maintained in media prepared with dc-DEP EMF force treated dilute saline while no growth inhibition occurred when the same cells were maintained in identically prepared but untreated media. Importantly, no growth inhibition was observed in human epithelial MCF-10A cells when grown in either treated or untreated media. Also, mitotic spindle formation was inhibited in the human breast carcinoma when they were grown in dc-DEP EMF force treated media. To determine if any gene expression changes contributed to the selective growth inhibition and absent mitotic spindle formation in the human breast carcinoma grown in the treated media, we employed microarray analysis and found that there was large-scale transcriptional reprogramming of the tumor cells grown in the treated media with over 1,000 genes up- or down-regulated over 2-fold, whereas the non-cancerous MCF-10A cells showed relatively modest changes in gene expression. Of the genes affected in the MDA-MB-231 cells, the significance of down-regulation of HMMR is discussed. The ability to enhance cell polarity through the application of this dc-DEP EMF force may offer another way to stabilize HMMR and differentially modulate its expression in cancerous and noncancerous cells.
调节癌细胞转移的机制通常与控制伤口修复中细胞迁移的机制紧密相连。透明质酸介导的运动受体（HMMR）编码一种透明质酸介导的运动（RHAMM）受体，它是一种非整合性细胞表面透明质酸受体和细胞内蛋白，可促进有丝分裂纺锤体形成和细胞运动。已发现RHAMM在癌症和伤口中表达均增加，并且当癌症中RHAMM表达增加时，会出现不良预后。因此，RHAMM已被证明对自然愈合机制和癌细胞病理都有作用。RHAMM在乳腺组织中表达，并与BRCA1形成极性归一化复合物。BRCA1的突变与顶基细胞极性丧失以及随后RHAMM表达增加有关。在此，我们展示了如何将人乳腺癌细胞系培养在用稀释盐溶液制备的培养基中，该稀释盐溶液已暴露于由3安培直流电（dc）产生的介电泳（DEP）电磁场（EMF）中，该电磁场作用于一个装有导电环阵列的装置。这种生物电场增强（BEFE）装置自1996年以来已在市场上销售，可用于浴缸/足浴，消费者声称它具有从降低血压到加速伤口愈合等多种健康益处。我们的研究表明，当人乳腺癌MDA - MB - 231细胞培养在用dc - DEP EMF力处理过的稀释盐溶液制备的培养基中时，其生长受到显著抑制，而当相同细胞培养在相同制备但未处理的培养基中时，未发生生长抑制。重要的是，人上皮MCF - 10A细胞在处理过或未处理的培养基中生长时，均未观察到生长抑制。此外，人乳腺癌细胞在dc - DEP EMF力处理过的培养基中生长时，有丝分裂纺锤体形成受到抑制。为了确定是否有任何基因表达变化导致了在处理过的培养基中生长的人乳腺癌细胞的选择性生长抑制和有丝分裂纺锤体形成缺失，我们采用了微阵列分析，发现处理过的培养基中生长的肿瘤细胞发生了大规模转录重编程，超过1000个基因上调或下调超过2倍，而非癌性MCF - 10A细胞的基因表达变化相对较小。在MDA - MB - 231细胞中受影响的基因中，讨论了HMMR下调的意义。通过施加这种dc - DEP EMF力来增强细胞极性的能力可能提供另一种稳定HMMR并在癌细胞和非癌细胞中差异调节其表达的方法。
