title: A complex pattern of chemokine receptor expression is seen in osteosarcoma.
abstract: BACKGROUND
  Osteosarcoma is the most frequent bone tumor in childhood and adolescence. Patients with primary metastatic disease have a poor prognosis. It is therefore important to better characterize the biology of this tumor to define new prognostic markers or therapeutic targets for tailored therapy. Chemokines and their receptors have been shown to be involved in the development and progression of malignant tumors. They are thought to be active participants in the biology of osteosarcoma. The function of specific chemokines and their receptors is strongly associated with the biological context and microenvironment of their expression. In this report we characterized the expression of a series of chemokine receptors in the complex environment that defines osteosarcoma.
  
  
  METHODS
  The overall level of chemokine receptor mRNA expression was determined using TaqMan RT-PCR of microdissected archival patient biopsy samples. Expression was then verified at the protein level by immunohistochemistry using a series of receptor specific antibody reagents to elucidate the cellular association of expression.
  
  
  RESULTS
  Expression at the RNA level was found for most of the tested receptors. CCR1 expression was found on infiltrating mononuclear and polynuclear giant cells in the tumor. Cells associated with the lining of intratumoral vessels were shown to express CCR4. Infiltrating mononuclear cells and tumor cells both showed expression of the receptor CCR5, while CCR7 was predominantly expressed by the mononuclear infiltrate. CCR10 was only very rarely detected in few scattered infiltrating cells.
  
  
  CONCLUSIONS
  Our data elucidate for the first time the cellular context of chemokine receptor expression in osteosarcoma. This is an important issue for better understanding potential chemokine/chemokine receptor function in the complex biologic processes that underlie the development and progression of osteosarcoma. Our data support the suggested involvement of chemokines and their receptors in diverse aspects of the biology of osteosarcoma, but also contradict aspects of previous reports describing the expression of these receptors in this tumor.
authors.affiliation: Children's Hospital Medical Center, University of Technology, Munich, Germany. irene.teichert-luettichau@lrz.tu-muenchen.de
authors.forename: Irene
authors.initials: I
authors.lastname: von Luettichau
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wechselberger
authors.forename: Mike
authors.initials: M
authors.lastname: Notohamiprodjo
authors.forename: Michaela
authors.initials: M
authors.lastname: Nathrath
authors.forename: Markus
authors.initials: M
authors.lastname: Kremer
authors.forename: Anna
authors.initials: A
authors.lastname: Henger
authors.forename: Roghieh
authors.initials: R
authors.lastname: Djafarzadeh
authors.forename: Stefan
authors.initials: S
authors.lastname: Burdach
authors.forename: Ralf
authors.initials: R
authors.lastname: Huss
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D019707:Receptors, Chemokine