c-Met 抑制对黑色素瘤细胞分子特征和转移潜力的影响。

IF 2 4区 医学 Q3 ONCOLOGY Neoplasma Pub Date : 2024-10-01 DOI:10.4149/neo_2024_240523N232
Lucia Demkova, Miroslava Matuskova, Katarina Gercakova, Zuzana Kozovska, Bozena Smolkova, Lucia Kucerova
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引用次数: 0

摘要

恶性黑色素瘤中肝细胞生长因子受体(c-Met)的异常激活与预后不良有关,会促进肿瘤进展、血管生成和侵袭性。虽然针对该通路的治疗已在多种肿瘤中显示出前景,但我们之前的研究结果表明,酪氨酸激酶抑制剂 SU11274 治疗后肿瘤致病性增加。因此,我们推测使用 c-Met 抑制剂可能会对人类黑色素瘤细胞产生不同的影响。在这项研究中,我们研究了三种c-Met抑制剂(SU11274、克唑替尼和PHA665752)对三种人类黑色素瘤细胞系(M4Beu、EGFP-A375及其转移变体EGFP-A375/Rel3(Rel3))的分子特征、致瘤性和转移行为的影响。克唑替尼和 PHA665752 可诱导 Rel3 细胞中的 MET 原癌基因、受体酪氨酸激酶 (MET)、癌症干细胞标志物 Prominin 1 (CD133)、多能性标志物 Nanog homeobox (Nanog),以及编码血管生成因子和受体的基因上调,这与对体内致瘤性的支持作用相关。SU11274处理后Rel3细胞致瘤性的增加与Akt、p70 S6和RSK激酶磷酸化的升高有关。我们的研究结果证明了小分子受体酪氨酸激酶抑制剂在黑色素瘤细胞系中诱导的多效应变化。
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The impact of c-Met inhibition on molecular features and metastatic potential of melanoma cells.

The aberrant activation of the hepatocyte growth factor receptor (c-Met) in malignant melanoma is associated with poor prognosis, fostering tumor progression, angiogenesis, and invasiveness. While therapeutic targeting of this pathway has shown promise in several tumors, our previous findings revealed increased tumorigenicity following tyrosine kinase inhibitor SU11274 treatment. Therefore, we hypothesized that administering c-Met inhibitors may elicit distinct effects in human melanoma cells. In this study, we investigated the influence of three c-Met inhibitors, SU11274, crizotinib, and PHA665752, on molecular characteristics, tumorigenicity, and metastatic behavior in three human melanoma cell lines, M4Beu, EGFP-A375 and its metastatic variant, EGFP-A375/Rel3 (Rel3). Crizotinib and PHA665752 induced upregulation of MET proto-oncogene, receptor tyrosine kinase (MET), alongside cancer stem cell marker Prominin 1 (CD133), pluripotency marker Nanog homeobox (Nanog), and genes encoding angiogenic factors and receptors in Rel3 cells, correlating with supportive effect on tumorigenicity in vivo. The increased tumorigenicity of the Rel3 cells following the SU11274 treatment correlated with the elevated phosphorylation of Akt, p70 S6 and RSK kinases. Our results demonstrate pleiotropic changes induced by small-molecule inhibitors of receptor tyrosine kinases in melanoma cell lines.

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来源期刊
Neoplasma
Neoplasma 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
238
审稿时长
3 months
期刊介绍: The journal Neoplasma publishes articles on experimental and clinical oncology and cancer epidemiology.
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