title: Strong expression of CXCL12 is associated with a favorable outcome in osteosarcoma.
abstract: Hematogenous spread determines the outcome of osteosarcoma (OS) patients, but the pathogenesis of developing metastatic disease is still unclear. Chemokines are critical regulators of cell trafficking and adhesion, and have been reported to be aberrantly expressed and to correlate with an unfavorable prognosis and metastatic spread in several malignant tumors. The chemokine receptors CXCR4 and CXCR7 together with their common ligand CXCL12 form one of the most important chemokine axes in this context. To investigate a potential role of these chemokines in OSs, we analyzed their expression in a series of 223 well-characterized and pretherapeutic OS samples. Interestingly, we found the expression of CXCL12 and CXCR4 to correlate with a better long-term outcome and with a lower prevalence of metastases. These findings suggest a distinct role of CXCR4/CXCR7/CXCL12 signaling in the tumors of bone, as has also been previously described in acute leukemia. As many malignant tumors metastasize to bone, and tumor cells are thought to be directed to bone in response to CXCL12, OS cells expressing both CXCL12 and the corresponding receptors might be detained at their site of origin. The disruption of CXCR4/CXCR7/CXCL12 signaling could therefore be crucial in OSs for the migration of tumor cells from bone into circulation and for developing systemic disease.
authors.affiliation: Bone Tumor Reference Center at the Institute of Pathology, University Hospital Basel, Basel, Switzerland. dbaumhoer@mac.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Baumhoer
authors.forename: Jan
authors.initials: J
authors.lastname: Smida
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zillmer
authors.forename: Michael
authors.initials: M
authors.lastname: Rosemann
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
authors.forename: Gernot
authors.initials: G
authors.lastname: Jundt
authors.forename: Irene
authors.initials: I
authors.lastname: von Luettichau
authors.forename: Michaela
authors.initials: M
authors.lastname: Nathrath
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D054377:Chemokine CXCL12 / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005858:Germany; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012516:Osteosarcoma / Q000276:immunology* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D054387:Receptors, CXCR / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D014746:Vimentin / Q000032:analysis; D055815:Young Adult
chemical_list: C501896:ACKR3 protein, human; D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D014746:Vimentin