Department of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, Netherlands.
Immunology. 2011 Jan;132(1):39-48. doi: 10.1111/j.1365-2567.2010.03335.x. Epub 2010 Aug 17.
Osteopontin (OPN) is a glycophosphoprotein with multiple intracellular and extracellular functions. In vitro, OPN enhances migration of mouse neutrophils and macrophages. In cancer, extracellular OPN facilitates migration of cancer cells via its RGD sequence. The present study was designed to investigate whether osteopontin is responsible for neutrophil and macrophage infiltration in human cancer and in particular in glioblastoma. We found that in vitro mouse neutrophil migration was RGD-dependent. In silico, we found that the OPN gene was one of the 5% most highly expressed genes in 20 out of 35 cancer microarray data sets in comparison with normal tissue in at least 30% of cancer patients. In some types of cancer, such as ovarian cancer, lung cancer and melanoma, the OPN gene was one of those with the highest expression levels in at least 90% of cancer patients. In glioblastoma, the most invasive type of brain tumours/glioma, but not in lower grades of glioma it was one of the 5% highest expressed genes in 90% of patients. In situ, we found increased protein levels of OPN in human glioblastoma versus normal human brain confirming in silico results. OPN protein expression was co-localized with neutrophils and macrophages. In conclusion, OPN in tumours not only induces migration of cancer cells but also of leucocytes.
骨桥蛋白（OPN）是一种具有多种细胞内和细胞外功能的糖磷蛋白。在体外，OPN 可增强小鼠中性粒细胞和巨噬细胞的迁移。在癌症中，细胞外 OPN 通过其 RGD 序列促进癌细胞的迁移。本研究旨在探讨骨桥蛋白是否负责人类癌症中中性粒细胞和巨噬细胞的浸润，尤其是在胶质母细胞瘤中。我们发现，体外小鼠中性粒细胞的迁移依赖于 RGD。在计算机模拟中，我们发现与至少 30%的癌症患者的正常组织相比，在 35 个癌症微阵列数据集的 20 个中，OPN 基因是前 5%表达最高的基因之一。在某些类型的癌症中，如卵巢癌、肺癌和黑色素瘤，OPN 基因是至少 90%的癌症患者中表达水平最高的基因之一。在胶质母细胞瘤中，即最具侵袭性的脑肿瘤/神经胶质瘤类型，但在较低级别胶质瘤中，它是 90%患者中前 5%表达最高的基因之一。在原位，我们发现人胶质母细胞瘤中 OPN 的蛋白水平升高，与计算机模拟结果一致。OPN 蛋白表达与中性粒细胞和巨噬细胞共定位。总之，肿瘤中的 OPN 不仅诱导癌细胞的迁移，还诱导白细胞的迁移。
