Upregulated expression of PDGF receptor beta in endocrine pancreatic tumors and metastases compared to normal endocrine pancreas.
Platelet-derived growth factor receptor (PDGFR) beta signaling is involved in autocrine growth stimulation of tumor cells, tumor angiogenesis and regulation of tumor interstitial fluid pressure. Development of PDGFR antagonists has further increased the interest for PDGFR as targets for anticancer treatments. Malignant endocrine pancreatic tumors (EPTs) express PDGFR beta both in stroma and on tumor cells. To investigate the role of PDGFR beta signaling in EPTs we compared PDGFR beta expression in normal endocrine pancreas to malignant EPTs and metastases. PDGFR beta expression was examined by immunohistochemistry using specific polyclonal antibodies in ten tissue samples from normal endocrine pancreas, 21 from primary EPTs and 19 from metastases. In eight patients we compared the expression in normal endocrine pancreas to the corresponding primary tumor and metastases, in two patients normal tissue to the primary tumor and in 11 patients primary tumors to the corresponding metastases. Six of ten tissues containing normal pancreas stained negative for PDGFR beta on endocrine cells, while seven of ten stained positive in the stroma. Eighteen of 21 (86%) primary tumors stained positive for PDGFR beta on tumor cells and all had positive stroma stainings. All 19 metastases stained positive for PDGFR beta on tumor cells and in evaluable stroma (n=16). We have found that PDGFR beta is more frequently expressed in primary EPTs and metastases as compared to normal endocrine pancreatic tissue. This is also true for PDGFR beta expression in the corresponding stroma. We suggest that new therapeutic options to inhibit the growth and spread of EPTs could include targeting of PDGFR beta.
Fjällskog
Marie-Louise
ML
Department of Oncology, University Hospital, Uppsala, Sweden. marie-louise.fjallskog@medsci.uu.se
Hessman
Ola
O
Eriksson
Barbro
B
Janson
Eva Tiensuu
ET
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004703:Endocrine System / Q000503:physiopathology*; D004700:Endocrine System Diseases / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D010179:Pancreas / Q000502:physiology / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000502:physiology*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D020797:Receptor, Platelet-Derived Growth Factor beta