TY - JOUR
T1 - Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft
AU - Bandyopadhyay, Abhik
AU - López-Casillas, Fernando
AU - Malik, Shazli N.
AU - Montiel, José Luis
AU - Mendoza, Valentín
AU - Yang, Junhua
AU - Sun, L. Z.
PY - 2002/8/15
Y1 - 2002/8/15
N2 - We have demonstrated previously that ectopic expression of a soluble betaglycan, also known as transforming growth factor (TGF) β type III receptor, can suppress the malignant properties of human carcinoma cells by antagonizing the tumor-promoting activity of TGF-β (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-β with high affinity and isoform selectivity and neutralized the activity of TGF-β1 in two bioassays. Peritumoral (50 μg/tumor, twice a week) or i.p. (100 μg/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-β.
AB - We have demonstrated previously that ectopic expression of a soluble betaglycan, also known as transforming growth factor (TGF) β type III receptor, can suppress the malignant properties of human carcinoma cells by antagonizing the tumor-promoting activity of TGF-β (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-β with high affinity and isoform selectivity and neutralized the activity of TGF-β1 in two bioassays. Peritumoral (50 μg/tumor, twice a week) or i.p. (100 μg/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-β.
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M3 - Article
C2 - 12183427
AN - SCOPUS:0037102289
VL - 62
SP - 4690
EP - 4695
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 16
ER -