University Health Network, Toronto General Hospital, Room 2-805, MaRS Tower, 101 College Street, Toronto, M5G 1L7, Canada.
Breast Cancer Res Treat. 2010 Sep;123(2):405-15. doi: 10.1007/s10549-009-0667-8. Epub 2009 Dec 2.
CD200 has been characterized as an important immunoregulatory molecule, increased expression of which can lead to decreased transplant rejection, autoimmunity, and allergic disease. Elevated CD200 expression has been reported to be associated with poor prognosis in a number of human malignancies. We have found that cells of the transplantable EMT6 mouse breast cancer line growing in vitro express low levels of CD200, but levels increase markedly during growth in immunocompetent mice. Similar increased in vivo expression does not occur in NOD-SCID.IL-2(gammar-/-) mice or mice with generalized over-expression of a CD200 transgene. In both mice, tumor growth occurs faster. Altered CD200 expression in control versus transgenic mice is accompanied by reproducible changes in tumor-infiltrating host cells, and altered cell composition in lymph nodes draining the tumor (DLN). Neutralization of expressed CD200 by anti-CD200mAbs leads to decreased tumor growth in immunocompetent mice, with improved detection of cytotoxic anti-tumor immune cells in DLN. Finally, we report that tumor growth in vivo can be monitored by levels of soluble CD200 (sCD200) in serum of tumor-bearing animals.
CD200 已被鉴定为一种重要的免疫调节分子，其表达增加可导致移植排斥、自身免疫和过敏疾病减少。据报道，在许多人类恶性肿瘤中，CD200 的高表达与预后不良有关。我们发现，在体外生长的可移植 EMT6 小鼠乳腺癌细胞系中的细胞表达低水平的 CD200，但在免疫功能正常的小鼠中生长时，其水平显著增加。在 NOD-SCID.IL-2(gammar-/-)小鼠或过表达 CD200 转基因的小鼠中，不会发生类似的体内表达增加。在这两种小鼠中，肿瘤生长更快。与对照转基因小鼠相比，CD200 表达的改变伴随着肿瘤浸润宿主细胞的可重复变化，以及引流肿瘤的淋巴结 (DLN) 中细胞成分的改变。用抗 CD200mAbs 中和表达的 CD200 可导致免疫功能正常的小鼠肿瘤生长减少，并改善 DLN 中细胞毒性抗肿瘤免疫细胞的检测。最后，我们报告说，通过荷瘤动物血清中的可溶性 CD200(sCD200)水平可以监测体内肿瘤的生长。
