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靶向放射性核素治疗通过改变上皮-间质转化样机制减少黑色素瘤肺侵袭。

Targeted Radionuclide Therapy Decreases Melanoma Lung Invasion by Modifying Epithelial-Mesenchymal Transition-Like Mechanisms.

作者信息

Akil Hussein, Rouanet Jacques, Viallard Claire, Besse Sophie, Auzeloux Philippe, Chezal Jean-Michel, Miot-Noirault Elisabeth, Quintana Mercedes, Degoul Françoise

机构信息

UMR 1240 INSERM, University of Clermont Auvergne, Clermont-Ferrand, France.

UMR 1240 INSERM, University of Clermont Auvergne, Clermont-Ferrand, France; Department of Dermatology and Oncodermatology, CHU Estaing, Clermont-Ferrand, France; Centre Jean Perrin, Clermont-Ferrand, France.

出版信息

Transl Oncol. 2019 Nov;12(11):1442-1452. doi: 10.1016/j.tranon.2019.07.015. Epub 2019 Aug 14.

DOI:10.1016/j.tranon.2019.07.015
PMID:31421458
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6704444/
Abstract

Melanin-radiolabeled molecules for targeted radionuclide therapy (TRT) provide a promising approach for the treatment of pigmented melanoma. Among these radiolabeled molecules, the iodinated melanin-specific binding molecule ([I]ICF01012) has shown a significant antitumor effect on metastatic melanoma preclinical models. We report herein that [I]ICF01012 decreases the epithelial-mesenshymal transition-like (EMT-like) markers in both in vivo and in vitro three-dimensional (3D) melanoma spheroid models. [I]ICF01012 spheroids irradiation resulted in reduced clonogenic capacity of all pigmented spheroids accompanied by increased protein expression levels of phosphorylated H2A.X, p53 and its downstream target p21. In addition, [I]ICF01012 treatment leads to a significant increase of cell pigmentation as demonstrated in SK-MEL3 human xenograft model. We also showed that [I]ICF01012 decreases the size and the number of melanoma lung colonies in the syngeneic murine B16BL6 in vivo model assessing its potentiality to kill circulating tumor cells. Taken together, these results indicate that [I]ICF01012 reduces metastatic capacity of melanoma cells presumably through EMT-like reduction and cell differentiation induction.

摘要

用于靶向放射性核素治疗（TRT）的黑色素放射性标记分子为色素沉着性黑色素瘤的治疗提供了一种很有前景的方法。在这些放射性标记分子中，碘化黑色素特异性结合分子（[I]ICF01012）在转移性黑色素瘤临床前模型中已显示出显著的抗肿瘤作用。我们在此报告，[I]ICF01012在体内和体外三维（3D）黑色素瘤球体模型中均可降低上皮-间质转化样（EMT样）标志物。[I]ICF01012球体照射导致所有色素沉着球体的克隆形成能力降低，同时磷酸化H2A.X、p53及其下游靶点p21的蛋白表达水平升高。此外，如在SK-MEL3人异种移植模型中所示，[I]ICF01012处理导致细胞色素沉着显著增加。我们还表明，在评估其杀死循环肿瘤细胞潜力的同基因小鼠B16BL6体内模型中，[I]ICF01012可减小黑色素瘤肺集落的大小并减少其数量。综上所述，这些结果表明，[I]ICF01012可能通过类似EMT的减少和细胞分化诱导来降低黑色素瘤细胞的转移能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/ad141ccb35e5/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/569d98fb55e6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/af3961bfec7d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/dd96ff65793b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/e2bd5c361943/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/ee085020bd9e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/1d75065b0c39/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/744f7b262168/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/7a4931e2f431/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/d1585dd43ccb/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/ad141ccb35e5/figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/569d98fb55e6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/af3961bfec7d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/dd96ff65793b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/e2bd5c361943/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/ee085020bd9e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/1d75065b0c39/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/744f7b262168/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/7a4931e2f431/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/d1585dd43ccb/figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/648a/6704444/ad141ccb35e5/figs2.jpg

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