a role for fibrillar collagen deposition and the collagen internalization receptor endo180 in glioma invasion胶原蛋白纤维沉积和胶原蛋白内化的作用受体在神经胶质瘤endo180入侵.pdfVIP

A Role for Fibrillar Collagen Deposition and the Collagen Internalization Receptor Endo180 in Glioma Invasion 1 1 2 1 3 2 Ivo J. Huijbers , Marjan Iravani , Sergey Popov , David Robertson , Safa Al-Sarraj , Chris Jones , Clare M. Isacke1* 1 Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom, 2 Paediatric Oncology, The Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, United Kingdom, 3 Clinical Neuropathology, King’s College Hospital, London, United Kingdom Abstract Background: Glioblastoma multiforme (GBM, WHO grade IV) is the most common and most malignant of astrocytic brain tumors, and is associated with rapid invasion into neighboring tissue. In other tumor types it is well established that such invasion involves a complex interaction between tumor cells and locally produced extracellular matrix. In GBMs, surprisingly little is known about the associated matrix components, in particular the fibrillar proteins such as collagens that are known to play a key role in the invasion of other tumor types. Methodology/Principal Findings: In this study we have used both the Masson’s trichrome staining and a high resolution multiple immunofluorescence labeling method to demonstrate that intratumoral fibrillar collagens are an integral part of the extracellular matrix in a subset of GBMs. Correlated with this collagen deposition we observed high level expression of the collagen-binding receptor Endo180 (CD280) in the tumor cells. Further, interrogation of multiple expression array datasets identified Endo180 as one of the most highly upregulated transcripts in grade IV GBMs compared to grade III gliomas. Using promoter analysis studies we show that this increased