Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft

Abhik Bandyopadhyay, Fernando López-Casillas, Shazli N. Malik, José Luis Montiel, Valentín Mendoza, Junhua Yang, Luzhe Sun

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103 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4690-4695
Number of pages6
JournalCancer Research
Volume62
Issue number16
StatePublished - Aug 15 2002

Fingerprint

Heterografts
Breast Neoplasms
Transforming Growth Factors
Neoplasms
Nude Mice
Therapeutics
betaglycan
Growth Factor Receptors
Growth
Microvessels
Blood Volume
Tumor Burden
Biological Assay
Protein Isoforms
Hemoglobins
Endothelial Cells
Neoplasm Metastasis
Carcinoma
Lung
Skin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bandyopadhyay, A., López-Casillas, F., Malik, S. N., Montiel, J. L., Mendoza, V., Yang, J., & Sun, L. (2002). Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. Cancer Research, 62(16), 4690-4695.

Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. / Bandyopadhyay, Abhik; López-Casillas, Fernando; Malik, Shazli N.; Montiel, José Luis; Mendoza, Valentín; Yang, Junhua; Sun, Luzhe.

In: Cancer Research, Vol. 62, No. 16, 15.08.2002, p. 4690-4695.

Research output: Contribution to journalArticle

Bandyopadhyay, A, López-Casillas, F, Malik, SN, Montiel, JL, Mendoza, V, Yang, J & Sun, L 2002, 'Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft', Cancer Research, vol. 62, no. 16, pp. 4690-4695.
Bandyopadhyay A, López-Casillas F, Malik SN, Montiel JL, Mendoza V, Yang J et al. Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. Cancer Research. 2002 Aug 15;62(16):4690-4695.
Bandyopadhyay, Abhik ; López-Casillas, Fernando ; Malik, Shazli N. ; Montiel, José Luis ; Mendoza, Valentín ; Yang, Junhua ; Sun, Luzhe. / Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. In: Cancer Research. 2002 ; Vol. 62, No. 16. pp. 4690-4695.
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