The immunosuppressive surface ligand CD200 augments the metastatic capacity of squamous cell carcinoma.
The immunosuppressive surface ligand CD200 augments the metastatic capacity of squamous cell carcinoma.
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DOI：
10.1158/0008-5472.can-09-4380
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发表时间：
2010-04-01
期刊：
影响因子：
11.2
通讯作者：
Owens DM
中科院分区：
文献类型：
--
作者：
Stumpfova M;Ratner D;Desciak EB;Eliezri YD;Owens DM
CD 200（OX-2）是一种细胞表面糖蛋白，通过其受体CD 200 R（主要在骨髓细胞上表达）抑制同种免疫和自身免疫反应，从而赋予免疫赦免。CD 200抑制骨髓细胞活化的能力对于维持正常组织稳态至关重要，但也可能增强迁移性肿瘤细胞的存活。我们发现，CD 200的表达在分化良好的原发性鳞状细胞癌（SCC）的皮肤基本上是不存在的，但高度诱导SCC转移到淋巴结和其他实体组织。CD 200不影响SCC细胞的增殖或侵袭能力或其重建原发性皮肤肿瘤的能力。然而，CD 200的缺失削弱了SCC细胞转移和接种继发性肿瘤的能力，表明CD 200 + SCC细胞的存活可能取决于它们与CD 200 R+免疫细胞相互作用的能力。CD 200 R+基质细胞的主要群体是CD 11b +Gr-1+髓源性抑制细胞（MDSC），当存在SCC细胞时，以CD 200依赖性方式释放升高水平的G-CSF和GM-CSF。总的来说，我们的研究结果暗示CD 200是SCC转移的标志，并表明CD 200 + SCC角质形成细胞直接参与和调节CD 200 R + MDSC的能力对转移性生存至关重要。
CD200 (OX-2) is a cell surface glycoprotein that imparts immune privilege by suppressing alloimmune and autoimmune responses through its receptor, CD200R, expressed primarily on myeloid cells. The ability of CD200 to suppress myeloid cell activation is critical for maintaining normal tissue homeostasis but may also enhance survival of migratory neoplastic cells. We show that CD200 expression is largely absent in well-differentiated primary squamous cell carcinoma (SCC) of the skin, but is highly induced in SCC metastases to the lymph node and other solid tissues. CD200 does not influence the proliferative or invasive capacity of SCC cells or their ability to reconstitute primary skin tumors. However, loss of CD200 impairs the ability of SCC cells to metastasize and seed secondary tumors, indicating that the survival of CD200+ SCC cells may depend on their ability to interact with CD200R+ immune cells. The predominant population of CD200R+ stromal cells were CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs), which release elevated levels of G-CSF and GM-CSF when in the presence of SCC cells in a CD200-dependent manner. Collectively, our findings implicate CD200 as a hallmark of SCC metastasis and suggest that the ability of CD200+ SCC keratinocytes to directly engage and modulate CD200R+ MDSCs is essential to metastatic survival.