Insulin-like growth factor binding protein-2 is a novel therapeutic target associated with breast cancer.
OBJECTIVE
Insulin-like growth factor (IGF) binding proteins (IGFBP) modulate interactions of IGF ligands with the IGF-I receptor. The role of IGFBPs, and specifically IGFBP-2, in breast cancer progression has been poorly defined. This study assesses the effect of IGFBP-2 on the behavior of human breast cancer using clinical specimens as well as in vitro and in vivo experimental systems.


METHODS
4,181 primary invasive breast cancers and 120 benign breast tissue samples were identified for tumor tissue microarray construction and immunostained with IGFBP-2 antibody. Estrogen receptor-negative MDA-MB-231 cells constitutively overexpressing IGFBP-2 (MDA-MB-231BP-2) were created to assess the effect of IGFBP-2 gain-of-function. MDA-MB-468 cells, naturally expressing IGFBP-2, were used to determine the effect of IGFBP-2 loss-of-function using OGX-225, an antisense oligonucleotide drug candidate.


RESULTS
IGFBP-2 expression was significantly higher in breast cancer tissue compared with benign breast tissue. MDA-MB-231BP-2 cells grew more rapidly and were more resistant to paclitaxel both in vitro and in vivo compared with parental cells. OGX-225 decreased IGFBP-2 expression and attenuated the associated aggressive phenotype of MDA-MB-231BP-2 cells both in vitro and in vivo. Furthermore, OGX-225 inhibited the in vitro and in vivo growth of MDA-MB-468 cells.


CONCLUSIONS
This study provides evidence that IGFBP-2 expression is associated with breast cancer. Novel therapeutics targeting IGFBP-2, such as OGX-225, merit further evaluation.
So
Alan I
AI
The Prostate Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada. alan.so@ubc.ca
Levitt
Randy J
RJ
Eigl
Bernhard
B
Fazli
Ladan
L
Muramaki
Motosugu
M
Leung
Sam
S
Cheang
Maggie C U
MC
Nielsen
Torsten O
TO
Gleave
Martin
M
Pollak
Michael
M
D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism / Q000502:physiology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D046888:Tissue Array Analysis
D018971:Insulin-Like Growth Factor Binding Protein 2; D020319:Oligodeoxyribonucleotides, Antisense