title: The Reed-Steinberg cell: molecular characterization by proteomic analysis with therapeutic implications.
abstract: OBJECTIVE
  To characterize Reed-Sternberg (R-S) cells by proteomic analysis in order to gain insight into the molecular pathways that control their growth and thereby to discern potential molecular interventions in Hodgkin's disease.
  
  
  METHODS
  Ten cases of the nodular sclerosing (NS) subtype and 4 cases of the lymphocyte-predominant (LP) subtype were studied. Immunohistochemical procedures were performed to detect the following antigens: CD20, CD30, c-kit, platelet-derived growth factor receptor (PDGFR)-alpha, cathepsin D, angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor, phosphorylated c-Jun N-terminal kinase (p-JNK), c-Jun, Ki-67, the latency-associated peptide (LAP) of transforming growth factor-beta 1 (TGF-beta1), and the TGF-beta receptor (TGF-betaRII). Immunoreactivities were scored from 0 to 3+ positivity using bright-field microscopy.
  
  
  RESULTS
  The tyrosine kinase signal transducer, PDGFR-alpha, the AT1 receptor transactivator, the p-JNK downstream effector, Ki-67, and proapoptoticTGF-1 (LAP) were detected in R-S cells of the NS and LP subtypes; companion dendritic cells expressed cathepsin D and ACE. Intranuclear c-Jun was present in the NS subtype and stronger immunoreactivity for TGF-betaRII was evident in the LP subtype.
  
  
  CONCLUSIONS
  These data corroborate observations in the literature, characterizing R-S cells as possessing molecular pathways that incorporate PDGFR-alpha signaling and angiotensin transactivation with a potential for growth inhibition through activation of TGF-beta1 and upregulation of its receptor. Specific therapies to target R-S cells in Hodgkin's disease might include ST1571, an AT1 receptor inhibitor, and retinoids.
authors.affiliation: Division of Laboratory Medicine, Geisinger Medical Center, Danville, Pennsylvania 17822-0131, USA. rebrown@geisinger.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
authors.forename: R Kamal
authors.initials: RK
authors.lastname: Nazmi
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D000809:Angiotensins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D020543:Proteome / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011945:Receptors, Angiotensin / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D000809:Angiotensins; D020543:Proteome; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D007703:Peptidyl-Dipeptidase A