Interleukin-34 sustains pro-tumorigenic signals in colon cancer tissue.
Interleukin-34 sustains pro-tumorigenic signals in colon cancer tissue.
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DOI：
10.18632/oncotarget.23289
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
Monteleone G
中科院分区：
文献类型：
--
作者：
Franzè E;Dinallo V;Rizzo A;Di Giovangiulio M;Bevivino G;Stolfi C;Caprioli F;Colantoni A;Ortenzi A;Grazia AD;Sica G;Sileri PP;Rossi P;Monteleone G
白细胞介素-34（IL-34）是一种由多种细胞产生的细胞因子，与巨噬细胞集落刺激因子受体（M-CSFR-1）和受体型蛋白酪氨酸磷酸酶ζ（PTP-z）结合，并控制骨髓细胞的分化、增殖和存活。各种类型的癌症过度表达IL-34，但细胞因子在结肠直肠癌（CRC）中的作用仍然未知。我们研究了IL-34在结直肠癌中的表达和功能作用。与匹配的正常/良性结肠样品相比，在CRC样品中观察到更显著的IL-34表达，并且这发生在RNA和蛋白质水平上。CRC组织样本的免疫组织化学分析显示，癌细胞和固有层单核细胞都过表达IL-34。此外，CRC细胞表达M-CSFR-1和PTP-z，因此表明CRC细胞可以响应于IL-34。事实上，用IL-34而不是用MSC 1刺激DLD-1癌细胞，可以增强细胞增殖和细胞侵袭，而不影响细胞存活。对IL-34促有丝分裂作用的细胞内信号的分析表明，细胞因子增强了ERK 1/2的活化，而ERK 1/2的药理学抑制消除了IL-34驱动的细胞增殖。一致地，用特异性IL-34反义寡核苷酸敲低HT-29细胞中的IL-34降低了ERK 1/2活化、细胞增殖并增强了细胞对奥沙利铂诱导的死亡的易感性。这是第一项显示CRC中IL-34上调的研究，并表明这种细胞因子在结肠肿瘤发生中的作用。
Interleukin-34 (IL-34), a cytokine produced by a wide range of cells, binds to the macrophage colony-stimulating factor receptor (M-CSFR-1) and receptor-type protein-tyrosine phosphatase zeta (PTP-z) and controls myeloid cell differentiation, proliferation and survival. various types of cancers over-express IL-34 but the role of the cytokine in colorectal cancer (CRC) remains unknown. We here investigated the expression and functional role of IL-34 in CRC. A more pronounced expression of IL-34 was seen in CRC samples as compared to matched normal/benign colonic samples and this occurred at both RNA and protein level. Immunohistochemical analysis of CRC tissue samples showed that both cancer cells and lamina propria mononuclear cells over-expressed IL-34. Additionally, CRC cells expressed both M-CSFR-1 and PTP-z, thus suggesting that CRC cells can be responsive to IL-34. Indeed, stimulation of DLD-1 cancer cells with IL-34, but not with MSCF1, enhanced the cell proliferation and cell invasion without affecting cell survival. Analysis of intracellular signals underlying the mitogenic effect of IL-34 revealed that the cytokine enhanced activation of ERK1/2 and pharmacologic inhibition of ERK1/2 abrogated IL-34-driven cell proliferation. Consistently, IL-34 knockdown in HT-29 cells with a specific IL-34 antisense oligonucleotide reduced ERK1/2 activation, cell proliferation and enhanced the susceptibility of cells to Oxaliplatin-induced death. This is the first study showing up-regulation of IL-34 in CRC and suggesting a role for this cytokine in colon tumorigenesis.
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影响因子：
7.8
作者：
Byrne, P V;Guilbert, L J;Stanley, E R
通讯作者：
Stanley, E R
促进巨噬细胞存活和功能的胚胎干细胞对于畸胎瘤的发展至关重要
影响因子：
7.3
作者：
Chen T;Wang X;Guo L;Wu M;Duan Z;Lv J;Tai W;Renganathan H;Didier R;Li J;Sun D;Chen X;He X;Fan J;Young W;Ren Y
通讯作者：
Ren Y
影响因子：
3.7
作者：
Belluco, C;Nitti, D;Jessup, JM
通讯作者：
Jessup, JM
影响因子：
4
作者：
Eda, Hiroyuki;Shimada, Hideaki;Monahan, Joseph B.
通讯作者：
Monahan, Joseph B.
影响因子：
6
作者：
Franze, Eleonora;Monteleone, Ivan;Monteleone, Giovanni
通讯作者：
Monteleone, Giovanni