Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth in the absence of immune cells
Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth in the absence of immune cells
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DOI：
10.1002/ijc.28375
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发表时间：
2014-01-15
影响因子：
6.4
通讯作者：
Rots, Marianne G.
中科院分区：
文献类型：
--
作者：
de Groote, Marloes L.;Kazemier, Hinke G.;Rots, Marianne G.
卵巢癌是一种难以治疗的癌症，由于诊断晚和治疗阻力大，5年生存率仅接近45%。在需要新的治疗方法的情况下，诱导细胞间黏附分子(ICAM)-1的表达可能是有意义的，因为ICAM-1在卵巢癌细胞中的表达低于健康卵巢细胞，并且与肿瘤致瘤性降低有关。虽然ICAM-1在肿瘤细胞上的表达对于吸引免疫细胞是重要的，但ICAM-1也可能诱导肿瘤的发生和化疗耐药。在卵巢癌中，ICAM-1的这种作用尚不清楚。在这里，我们研究了ICAM-1是否通过使用ICAM靶向的人工转录因子双向调节ICAM-1的表达来发挥细胞生物学作用。对于一组卵巢癌细胞，评估肿瘤生长和顺铂敏感性。诱导ICAM-1的表达(在mRNA水平上是3到228倍，在蛋白质水平上是1.7到108倍)导致卵巢癌细胞生长减少和顺铂敏感性降低。MRNA水平的抑制率为48%~94%，蛋白质水平的抑制率为47%~91%。这项研究表明，除了其既定的免疫原性作用外，ICAM-1还影响卵巢癌细胞的细胞生物学行为，重要的是，通过人工转录因子的重新表达代表了一种有效的方法，用于验证在癌症中表观遗传沉默的基因，如ICAM-1。
Ovarian cancer is a difficult-to-treat cancer with a 5-year survival rate of only approximate to 45%, due to late diagnosis and therapy resistance. In need of new therapeutic approaches, induction of intercellular adhesion molecule (ICAM)-1 expression might be of interest, since the expression of ICAM-1 is lower in ovarian cancer cells compared with healthy ovarian cells and correlated with decreased tumorigenicity. Whereas ICAM-1 expression on tumor cells is of importance for attracting immune cells, ICAM-1 might also induce tumorigenicity and chemoresistance. In ovarian cancer, such a role of ICAM-1 is unclear. Here, we investigated whether ICAM-1 has a cell-biological role by bidirectional modulation of ICAM-1 expression using ICAM-targeting artificial transcription factors. For a panel of ovarian cancer cells, tumor growth and cisplatin sensitivity were evaluated. Induction of ICAM-1 expression (ranging from 3- to 228-fold on mRNA level and 1.7- to 108-fold on protein level) resulted in indications of decreased ovarian cancer cell growth and reduced cisplatin sensitivity. Repression ranged from 48 to 94% on mRNA level and 47 to 91% on protein level. This study shows that, next to its established immunogenic role, ICAM-1 affects cell biological behavior of ovarian cancer cells and, importantly, that reexpression by artificial transcription factors represents a powerful approach for functional validation of genes epigenetically silenced in cancer, such as ICAM-1.