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Extracellular domain of TGFβ type III receptor inhibits angiogenesis and tumor growth in human cancer cells

Oncogene volume 21, pages 3541–3551 (2002)Cite this article

Abstract

TGFβ overexpression in human cancer cells has been shown to promote tumor progression. In the present study, we sought to determine whether sequestration of endogenous TGFβ by the expression of a soluble TGFβ type III receptor (sRIII), can reduce malignancy in human carcinoma cells and whether the tumor-suppressive activity of sRIII is associated with the inhibition of angiogenesis. Ectopic expression of sRIII significantly inhibited the growth of tumors formed by human colon carcinoma HCT116 and breast carcinoma MDA-MB-435 cells in nude mice. It also reduced the metastatic potential of the MDA-MB-435 cells. Thus, endogenous TGFβ appears to be necessary for the progression of these two carcinomas. Furthermore, when the tumor cells were mixed with Matrigel and embedded subcutaneously in nude mice, the blood volume in Matrigel plugs containing sRIII-expressing cells as indicated by hemoglobin levels was significantly lower than that in Matrigel plugs containing the respective control cells. Blood vessel counts in paraffin sections of the Matrigel plugs containing sRIII-expressing cells were also significantly lower than those in paraffin sections of the Matrigel plugs containing control cells. Treatment of human endothelial cells with a recombinant sRIII significantly inhibited their ability to form a capillary web structure on Matrigel. These results for the first time indicate that the sRIII-induced tumor suppression appears to be in part due to the inhibition of angiogenesis.

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Acknowledgements

We thank Dr Janet Price for giving us MDA-MB-435 cells. F Lopez-Casíllas is an International Research Scholar of the Howard Hughes Medical Institute. This work was supported by NIH Grants CA75253 and CA79683 to L-Z Sun and CA50457 and CA72001 to MG Brattain.

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Author notes

  1. Michael G Brattain

    Present address: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm &, Carlton Streets, Buffalo, New York, 14263, USA

Authors and Affiliations

  1. Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, 78229, Texas, TX, USA

    Abhik Bandyopadhyay, Yong Zhu & L-Z Sun

  2. Department of Surgery, University of Texas Health Science Center, San Antonio, 78229, Texas, TX, USA

    Shazli N Malik, Jeffrey Kreisberg & Michael G Brattain

  3. Department of Radiology, University of Texas Health Science Center, San Antonio, 78229, Texas, TX, USA

    Eugene A Sprague & Jian Luo

  4. Departmento de Biologia Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Fernando López-Casillas

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  1. Abhik Bandyopadhyay
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Correspondence to L-Z Sun.

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Bandyopadhyay, A., Zhu, Y., Malik, S. et al. Extracellular domain of TGFβ type III receptor inhibits angiogenesis and tumor growth in human cancer cells. Oncogene 21, 3541–3551 (2002). https://doi.org/10.1038/sj.onc.1205439

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