title: Proteomic detection of a large amount of SCGFα in the stroma of GISTs after imatinib therapy.
abstract: BACKGROUND
  Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors to develop in the digestive tract. These tumors are highly resistant to conventional chemotherapy and only the introduction of imatinib mesylate has improved the prognosis of patients. However, Response Evaluation Criteria in Solid Tumors are inappropriate for assessing tumor response, and the histological/pathological response to imatinib is variable, heterogeneous, and does not associate with clinical response. The effects of imatinib on responding GISTs are still being explored, and few studies correlate the clinical response with the histological response after pharmacological treatment. Recently, apoptosis and autophagy were suggested as possible alternative mechanisms of pharmacological response.
  
  
  METHODS
  Here, we used a proteomic approach, combined with other analyses, to identify some molecular stromal components related to the response/behavior of resected, high-risk GISTs after neoadiuvant imatinib therapy.
  
  
  RESULTS
  Our proteomic results indicate an elevated concentration of Stem Cell Growth Factor (SCGF), a hematopoietic growth factor having a role in the development of erythroid and myeloid progenitors, in imatinib-responsive tumor areas. SCGFα expression was detected by mass spectrometry, immunohistochemistry and/or western blot and attributed to acellular matrix of areas scored negative for KIT (CD117). RT-PCR results indicated that GIST samples did not express SCGF transcripts. The recently reported demonstration by Gundacker et al. 1 of the secretion of SCGF in mature pro-inflammatory dendritic cells would indicate a potential importance of SCGF in tissue inflammatory response. Accordingly, inflammatory infiltrates were detected in imatinib-affected areas and the CD68-positivity of the SCGF-positive and KIT-negative areas suggested previous infiltration of monocytes/macrophages into these regions. Thus, chronic inflammation subsequent to imatinib treatment may determine monocyte/macrophage recruitment in imatinib-damaged areas; these areas also feature prominent tumor-cell loss that is replaced by dense hyalinization and fibrosis.
  
  
  CONCLUSIONS
  Our studies highlight a possible role of SCGFα in imatinib-induced changes of GIST structure, consistent with a therapeutic response.
authors.affiliation: Proteomics Laboratory, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Da Riva
authors.forename: Fabio
authors.initials: F
authors.lastname: Bozzi
authors.forename: Piera
authors.initials: P
authors.lastname: Mondellini
authors.forename: Francesca
authors.initials: F
authors.lastname: Miccichè
authors.forename: Elena
authors.initials: E
authors.lastname: Fumagalli
authors.forename: Elena
authors.initials: E
authors.lastname: Vaghi
authors.forename: Eva
authors.initials: E
authors.lastname: Tarantino
authors.forename: Veronica
authors.initials: V
authors.lastname: Huber
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
authors.forename: Italia
authors.initials: I
authors.lastname: Bongarzone
mesh_terms: D001549:Benzamides; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000627:therapeutic use*; D040901:Proteomics / Q000379:methods*; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D001549:Benzamides; C110532:CLEC11A protein, human; D016298:Hematopoietic Cell Growth Factors; D037181:Lectins, C-Type; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate