肿瘤细胞治疗研究
英文原题：Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells-EGFRvIII Appears as a Weak Oncogene.
Phenotypical Flexibility of the EGFRvIII-Positive Glioblastoma Cell Line and the Multidirectional Influence of TGFβ and EGF on These Cells-EGFRvIII Appears as a Weak Oncogene.
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TGF 和 EGF 在 EGFRvIII 背景下的作用仍不明确。
表皮生长因子受体变体III（EGFRvIII）的生物学作用尚不明确。
研究人员使用表皮生长因子（EGF）和转化生长因子β（TGF-β）处理3种胶质母细胞瘤DK-MG亚系。这些亚系按EGFRvIII阳性细胞比例和倍增时间（从DK-MG低表达至特高表达）、扩增子数量及EGFRvIII mRNA表达水平进行表征，并评估生长因子对原代EGFRvIII阳性胶质母细胞瘤的影响。
在DK-MG高表达亚系中过表达外源EGFRvIII，并未使其转化为特高表达亚系，也未使低表达亚系转为高表达；而RAS G12V过表达可提高低表达亚系的增殖。尽管特高表达亚系中的EGFRvIII磷酸化水平最高，却未引起明显AKT（蛋白激酶B）和ERK（细胞外信号调节激酶）活化。进一步分析显示，TGF-β可诱导DK-MG高表达细胞凋亡；该亚系能够转化为特高表达亚系，而后者似乎对这种促凋亡作用耐受。EGF可促进细胞存活和增殖，但其是否同时诱导特高表达亚系衰老尚不明确。原代EGFRvIII阳性（SOX2阳性或阴性）胶质母细胞瘤细胞对EGF和TGF-β的应答各不相同。
TGF-β和EGF在EGFRvIII背景下的作用仍不明确。EGFRvIII似乎只是弱致癌基因，也不是胶质瘤干细胞（GSC）的标志物，因此可能不是合适的CAR-T 治疗靶点。
The biological role of EGFRvIII (epidermal growth factor receptor variant three) remains unclear.
Three glioblastoma DK-MG sublines were tested with EGF (epidermal growth factor) and TGF (transforming growth factor ). Sublines were characterized by an increased percentage of EGFRvIII-positive cells and doubling time (DK-MG low to DK-MG extra-high ), number of amplicons, and EGFRvIII mRNA expression. The influence of the growth factors on primary EGFRvIII positive glioblastomas was assessed.
The overexpression of exoEGFRvIII in DK-MG high did not convert them into DK-MG extra-high , and this overexpression did not change DK-MG low to DK-MG high ; however, the overexpression of RAS G12V increased the proliferation of DK-MG low . Moreover, the highest EGFRvIII phosphorylation in DK-MG extra-high did not cause relevant AKT (known as protein kinase B) and ERK (extracellular signal-regulated kinase) activation. Further analyses indicate that TGF is able to induce apoptosis of DK-MG high cells. This subline was able to convert to DK-MG extra-high , which appeared resistant to this proapoptotic effect. EGF acted as a pro-survival factor and stimulated proliferation; however, simultaneous senescence induction in DK-MG extra-high cells was ambiguous. Primary EGFRvIII positive (and SOX2 (SRY-Box Transcription Factor 2) positive or SOX2 negative) glioblastoma cells differentially responded to EGF and TGF .
The roles of TGF and EGF in the EGFRvIII context remain unclear. EGFRvIII appears as a weak oncogene and not a marker of GSC (glioma stem cells). Hence, it may not be a proper target for CAR-T (chimeric antigen receptor T cells).
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