Journal article
IGFBP-3 is a metastasis suppression gene in prostate cancer
Cancer research (Chicago, Ill.), Vol.71(15), pp.5154-5163
08/01/2011
DOI: 10.1158/0008-5472.CAN-10-4513
PMID: 21697285
Abstract
The insulin-like growth factor binding protein IGFBP-3 is a proapoptotic and antiangiogenic protein in prostate cancer (CaP). Epidemiologic studies suggest that low IGFBP-3 is associated with greater risk of aggressive, metastatic prostate cancers, but in vivo functional data are lacking. Here we show that mice that are genetically deficient in IGFBP-3 exhibit weaker growth of primary prostate tumors but higher incidence of metastatic disease. Prostates in IGFBP-3 knockout mice (IGFBP-3KO mice) failed to undergo apoptosis after castration. Spontaneous prostate tumors did not develop in IGFBP-3KO mice, but splenic lymphomas occurred in 23% of female IGFBP-3KO mice by 80 weeks of age. To assess the effects of IGFBP-3 deficiency on prostate cancer development, we crossed IGFBP-3KO mice with a c-Myc–driven model of CaP that develops slow-growing, nonmetastatic tumors. By 24 weeks of age, well-differentiated prostate cancers were observed in all mice regardless of IGFBP-3 status. However, by 80 weeks of age IGFBP-3KO mice tended to exhibit larger prostate tumors than control mice. More strikingly, lung metastases were observed at this time in 55% of the IGFBP-3KO mice but none in the control animals. Cell lines established from IGFBP-3KO:Myc tumors displayed more aggressive phenotypes in proliferation, invasion, and colony formation assays, relative to control Myc tumor cell lines. In addition, Myc:IGFBP-3KO cells exhibited evidence of epithelial–mesenchymal transition. Our findings established a function for IGFBP-3 in suppressing metastasis in prostate cancer, and they also offered the first reported transgenic model of spontaneous metastatic prostate cancer for studies of this advanced stage of disease.
Details
- Title: Subtitle
- IGFBP-3 is a metastasis suppression gene in prostate cancer
- Creators
- Hemal H. Mehta - Mattel Children's HospitalQinglei Gao - Mattel Children's HospitalColette Galet - Mattel Children's HospitalVladislava Paharkova - Mattel Children's HospitalJunxiang Wan - Mattel Children's HospitalJonathan Said - Mattel Children's HospitalJoanne J. Sohn - Mattel Children's HospitalGregory Lawson - Mattel Children's HospitalPinchas Cohen - Mattel Children's HospitalLaura J. Cobb - Mattel Children's HospitalKuk Wha Lee - Mattel Children's Hospital
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.71(15), pp.5154-5163
- DOI
- 10.1158/0008-5472.CAN-10-4513
- PMID
- 21697285
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Number of pages
- 10
- Grant note
- R01CA100938 / National Cancer Institute (http://data.elsevier.com/vocabulary/SciValFunders/100000054)
- Language
- English
- Date published
- 08/01/2011
- Academic Unit
- Injury Prevention Research Center; University of Iowa Health Care
- Record Identifier
- 9985137928502771
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