We have demonstrated previously that ectopic expression of a soluble
betaglycan, also known as
transforming growth factor (
TGF) beta type III receptor, can suppress the malignant properties of human
carcinoma cells by antagonizing the
tumor-promoting activity of
TGF-beta (A. Bandyopadhyay et al.,
Cancer Res., 59: 5041-5046, 1999). In the current study, we investigated the potential therapeutic utility of a recombinant preparation of human and rat soluble
betaglycan (sBG). Purified recombinant human sBG showed similar properties to its rat counterpart (M. M. Vilchis-Landeros et al., Biochem J., 355: 215-222, 2001). It bound
TGF-beta with high affinity and
isoform selectivity and neutralized the activity of TGF-beta(1) in two bioassays. Peritumoral (50 micro g/
tumor, twice a week) or i.p. (100 micro g/animal, every alternate day) injection of sBG into human
breast carcinoma MDA-MB-231 xenograft-bearing athymic nude mice significantly inhibited the
tumor growth. The administration of sBG also reduced metastatic incidence and colonies in the lungs. The
tumor-inhibitory activity of sBG was found to be associated with the inhibition of angiogenesis. Systemic sBG treatment significantly reduced
tumor microvessel density detected with histological analyses and CD-31 immunostainings, as well as
tumor blood volume measured with
hemoglobin content. In an in vitro angiogenesis assay, treatment with the recombinant sBG significantly reduced the ability of human dermal microvascular endothelial cells to form a capillary tube-like structure on
Matrigel. These findings support the conclusion that sBG treatment suppresses
tumor growth and
metastasis, at least in part by inhibiting angiogenesis. As such, it could be a useful therapeutic agent to antagonize the
tumor-promoting activity of
TGF-beta.