ENHANCED METASTATIC ABILITY OF TNF-ALPHA-TREATED MALIGNANT-MELANOMA CELLS IS REDUCED BY INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1, CD54) ANTISENSE OLIGONUCLEOTIDES
ENHANCED METASTATIC ABILITY OF TNF-ALPHA-TREATED MALIGNANT-MELANOMA CELLS IS REDUCED BY INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1, CD54) ANTISENSE OLIGONUCLEOTIDES
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DOI：
10.1006/excr.1994.1253
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发表时间：
1994-09-01
影响因子：
3.7
通讯作者：
WELCH, DR
中科院分区：
文献类型：
--
作者：
MIELE, ME;BENNETT, CF;WELCH, DR
用肿瘤坏死因子-α（TNF-α）或干扰素-γ（IFN-γ）处理人恶性黑素瘤细胞导致ICAM-1表面表达的剂量和时间依赖性增加。ICAM-1表达增加对应于表达人白细胞功能抗原-1（CD 11 a/CD 18）的外周血单核细胞（PBMC）与C8161单层的结合增强，表明经苦参碱处理的黑色素瘤细胞由于PBMC-肿瘤细胞栓塞而更具转移性。本研究的目的是：（1）测试TNF-α处理的人黑素瘤细胞是否确实比未处理的C8161更具转移性和（2）确定ICAM-1是否在C8161的转移中起作用。当表面ICAM-1表达上调时，人黑色素瘤细胞系C8161、MeWo和A375在裸小鼠中肺转移的形成增加1.5至4倍（P < 0.05）。通过ELISA和流式细胞术测定，使用阳离子脂质用ICAM-1硫代磷酸酯反义寡核苷酸处理C8161导致>90%的ICAM-1表面表达抑制。反义ICAM-1处理的细胞形成的转移比假处理的细胞少41-64%。当反义处理的黑素瘤细胞暴露于TNF-α时，转移不会增加。然而，用反义5-脂氧合酶（5-LO）寡核苷酸处理C8161可抑制Lipofectin处理细胞中39%的转移，但不能抑制TNF-α诱导的实验转移上调。进行类似的实验来测量PBMC与反义阿托伐他汀处理的C8161细胞的粘附;然而，TNF-α诱导的粘附增加不受ICAM-1或5-LO反义寡核苷酸的影响。这些结果表明，ICAM-1参与黑色素瘤转移，但可能不是在PBMC粘附到C8161细胞的步骤。(C)1994年出版社出版。
Treating human malignant melanoma cells with tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) causes a dose- and time-dependent increase in surface expression of ICAM-1. Increased ICAM-1 expression corresponds to greater binding of human leukocyte functional antigen-1 (CD11a/CD18)-expressing peripheral blood mononuclear cells (PBMC) to C8161 monolayers, suggesting that cytokine-treated melanoma cells would be more metastatic due to PBMC-tumor cell emboli. The purpose of this study was: (1) to test whether TNF-alpha-treated human melanoma cells are indeed more metastatic than untreated C8161 and (2) to determine whether ICAM-1 plays a role in metastasis of C8161. When surface ICAM-1 expression is upregulated, formation of lung metastases in nude mice increases 1.5- to 4-fold (P < 0.05) for human melanoma cell lines C8161, MeWo, and A375. Treatment of C8161 with ICAM-1 phosphorothioate antisense oligonucleotides using cationic lipids results in >90% inhibition of ICAM-1 surface expression as determined by ELISA and flow cytometry. Antisense ICAM-1-treated cells form 41-64% fewer metastases than sham-treated cells. Metastasis does not increase when antisense-treated melanoma cells are exposed to TNF-alpha. However, treatment of C8161 with antisense 5-lipoxygenase (5-LO) oligonucleotides inhibits metastases 39% in Lipofectin-treated cells, but does not inhibit TNF-alpha-induced upregulation of experimental metastases. Similar experiments were performed to measure PBMC adhesion to antisense oligonucleotide-treated C8161 cells; however, TNF-alpha-inducible increase in adhesion was unaffected by ICAM-1 or 5-LO antisense oligonucleotides. These results demonstrate that ICAM-1 is involved in melanoma metastasis, but probably not at the step of PBMC adhesion to C8161 cells. (C) 1994 Academic Press, Inc.