title: Osteopontin is up-regulated and associated with neutrophil and macrophage infiltration in glioblastoma.
abstract: 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.
authors: Department of Cell Biology and Histology, Academic Medical Centre, University of Amsterdam, Netherlands.
authors: Nadia A
authors: NA
authors: Atai
authors: Manju
authors: M
authors: Bansal
authors: Cheungh
authors: C
authors: Lo
authors: Joost
authors: J
authors: Bosman
authors: Wikky
authors: W
authors: Tigchelaar
authors: Klazien S
authors: KS
authors: Bosch
authors: Ard
authors: A
authors: Jonker
authors: Philip C
authors: PC
authors: De Witt Hamer
authors: Dirk
authors: D
authors: Troost
authors: Christopher A
authors: CA
authors: McCulloch
authors: Vincent
authors: V
authors: Everts
authors: Cornelis J F
authors: CJ
authors: Van Noorden
authors: Jaro
authors: J
authors: Sodek
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009154:Mutation; D009504:Neutrophils / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D053495:Osteopontin