Merck

An antimetastatic role for decorin in breast cancer.

The American journal of pathology (2008-08-09)
Silvia Goldoni, Daniela G Seidler, Jack Heath, Matteo Fassan, Raffaele Baffa, Mathew L Thakur, Rick T Owens, David J McQuillan, Renato V Iozzo
ABSTRACT

Decorin, a member of the small leucine-rich proteoglycan gene family, down-regulates members of the ErbB receptor tyrosine kinase family and attenuates their signaling, leading to growth inhibition. We investigated the effects of decorin on the growth of ErbB2-overexpressing mammary carcinoma cells in comparison with AG879, an established ErbB2 kinase inhibitor. Cell proliferation and anchorage-independent growth assays showed that decorin was a potent inhibitor of breast cancer cell growth and a pro-apoptotic agent. When decorin and AG879 were used in combination, the inhibitory effect was synergistic in proliferation assays but only additive in both colony formation and apoptosis assays. Active recombinant human decorin protein core, AG879, or a combination of both was administered systemically to mice bearing orthotopic mammary carcinoma xenografts. Primary tumor growth and metabolism were reduced by approximately 50% by both decorin and AG879. However, no synergism was observed in vivo. Decorin specifically targeted the tumor cells and caused a significant reduction of ErbB2 levels in the tumor xenografts. Most importantly, systemic delivery of decorin prevented metastatic spreading to the lungs, as detected by novel species-specific DNA detection and quantitative assays. In contrast, AG879 failed to have any effect. Our data support a role for decorin as a powerful and effective therapeutic agent against breast cancer due to its inhibition of both primary tumor growth and metastatic spreading.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fetal Bovine Serum, USDA approved, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, Canada origin, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, Heat Inactivated, non-USA origin, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, USA origin, Charcoal Stripped, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, USA origin, sterile-filtered, suitable for cell culture, suitable for hybridoma
Sigma-Aldrich
Fetal Bovine Serum, USA origin, Heat Inactivated, sterile-filtered, suitable for cell culture, suitable for insect cell culture, suitable for hybridoma
Sigma-Aldrich
Fetal Bovine Serum, USA origin, Dialyzed by ultrafiltration against 0.15 M NaCl, sterile-filtered, suitable for cell culture
SAFC
Fetal Bovine Serum, Australia origin, γ-irradiated, suitable for cell culture, suitable for hybridoma
Sigma-Aldrich
Fetal Bovine Serum, Australia origin, suitable for, USDA approved, sterile-filtered, suitable for cell culture, suitable for hybridoma
Sigma-Aldrich
Fetal Bovine Serum, non-USA origin, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, USA origin, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, non-USA origin, from USDA approved countries, Heat Inactivated, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, USA origin, γ-irradiated by SER-TAIN process, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, Australia origin, γ-irradiated, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, USA origin, Heat Inactivated, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, Australia origin, USDA approved, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Fetal Bovine Serum, Australia origin, USDA approved, Heat Inactivated, suitable for cell culture