MDSCs are involved in the protumorigenic potentials of GM-CSF in colitis-associated cancer.
MDSCs are involved in the protumorigenic potentials of GM-CSF in colitis-associated cancer.
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DOI：
10.1177/0394632017711055
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发表时间：
2017-06
影响因子：
3.5
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Ma N;Liu Q;Hou L;Wang Y;Liu Z
慢性炎症被认为是结肠炎相关性结直肠癌(CAC)发展的主要驱动力。粒细胞巨噬细胞集落刺激因子(GM-CSF)作为促炎细胞因子家族的一员，近年来被证实在CAC的发病机制中起着关键作用。然而，潜在的机制在很大程度上仍然不为人知。在这项研究中，我们发现在从结肠炎到癌症的发展过程中，髓系来源的抑制细胞(MDSCs)在病变中积累越来越多，这对CAC的形成至关重要。重要的是，这种MDSC的聚集是由GM-CSF控制的。经CAC诱导后，GM-CSF缺陷小鼠的MDSC数量显著减少，将野生型CAC小鼠的MDSC输注到GM-CSF缺陷小鼠体内可导致CAC复发。此外，仅CAC病变或GM-CSF的上清液就足以将造血祖细胞分化为MDSCs。加入中和抗GM-CSF抗体可削弱CAC病变上清液对MDSC的分化作用。总体而言，这些发现通过诱导/招募促进CAC的MDSC，为了解GM-CSF在CAC发生中的作用机制提供了新的见解。阻断GM-CSF活性或MDSC功能可能代表CAC临床治疗的新策略。
Chronic inflammation is thought to be a major driving force for the development of colitis-associated colorectal cancer (CAC). As one member of proinflammatory cytokine family, granulocyte macrophage colony-stimulating factor (GM-CSF) has been identified to play a key role in CAC pathogenesis recently. The underlying mechanisms, however, remain largely unknown. In this study, we found that myeloid-derived suppressor cells (MDSCs) accumulated increasingly in the lesions during the progression from colitis to cancer, which was critical for CAC formation. Importantly, this MDSC accumulation was controlled by GM-CSF. MDSC number decreased significantly in GM-CSF-deficient mice suffering from CAC induction, and transfusion of MDSCs from wild-type CAC-bearing mice into GM-CSF-deficient counterparts led to recurrence of CAC. Furthermore, the supernatants of CAC lesions or GM-CSF alone was sufficient to differentiate hematopoietic precursors into MDSCs. Addition of neutralizing anti-GM-CSF antibody impaired the MDSC-differentiating effects of the supernatants of CAC lesions. Overall, these findings shed new insights into the mechanisms of GM-CSF underlying CAC development, by inducing/recruiting CAC-promoting MDSCs. Blocking GM-CSF activity or MDSC function may represent new therapeutic strategies for CAC in clinic.
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影响因子：
11.2
作者：
Serafini, P;Carbley, R;Borrello, I
通讯作者：
Borrello, I
DOI：
10.1084/jem.20080132
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cheng P;Corzo CA;Luetteke N;Yu B;Nagaraj S;Bui MM;Ortiz M;Nacken W;Sorg C;Vogl T;Roth J;Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
56.9
作者：
DRANOFF, G;CRAWFORD, AD;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
影响因子：
50.3
作者：
Grivennikov S;Karin E;Terzic J;Mucida D;Yu GY;Vallabhapurapu S;Scheller J;Rose-John S;Cheroutre H;Eckmann L;Karin M
通讯作者：
Karin M
影响因子：
4.1
作者：
Tcherkas, YV;Kartsova, LA;Krasnova, IN
通讯作者：
Krasnova, IN