Insulin-like growth factor 1 receptor is a prognostic factor in classical Hodgkin lymphoma.
The interaction between the tumor cells in classical Hodgkin lymphoma (cHL) and the microenvironment includes aberrant activity of receptor tyrosine kinases. In this study we evaluated the expression, functionality and prognostic significance of Insulin-like growth factor-1 receptor (IGF-1R) in cHL. IGF-1R was overexpressed in 55% (44/80) of cHL patients. Phosphorylated IGF-1R was detectable in a minority of the IGF-1R positive tumor cells. The overall survival (OS, 98%) and 5-year progression-free survival (PFS, 93%) was significantly higher in IGF-1R positive cHL patients compared to IGF-1R negative patients (OS 83%, p = .029 and PFS 77%, p = .047, respectively). Three cHL cell lines showed expression of IGF-1R, with strong staining especially in the mitotic cells and expression of IGF-1. IGF-1 treatment had a prominent effect on the cell growth of L428 and L1236 cells and resulted in an increased phosphorylation of IGF1R, Akt and ERK. Inhibition of IGF-1R with cyclolignan picropodophyllin (PPP) decreased cell growth and induced a G2/M cell cycle arrest in all three cell lines. Moreover, a decrease in pCcd2 and an increase in CyclinB1 levels were observed which is consistent with the G2/M cell cycle arrest. In conclusion, IGF-1R expression in HRS cells predicts a favorable outcome, despite the oncogenic effect of IGF-1R in cHL cell lines.
Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands ; Laboratory of Cancer Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China ; Department of Otolaryngology, Tianjin Medical University General Hospital, Tianjin, China.
Zheng
Z
Liang
Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Arjan
A
Diepstra
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
Chuanhui
C
Xu
Department of Hematology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Gustaaf
G
van Imhoff
Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Wouter
W
Plattel
Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Anke
A
Van Den Berg
Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Lydia
L
Visser
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006689:Hodgkin Disease / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D059016:Tumor Microenvironment
C415032:picropodophyllin; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin