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Analyses of the role of endogenous SPARC in mouse models of prostate and breast cancer

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Abstract

Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin or BM-40) is a glycoprotein component of the extracellular matrix that has been reported to be involved with a variety of cellular processes. Although SPARC expression levels are frequently altered in a variety of tumor types, the exact implications of deregulated SPARC expression—whether it promotes, inhibits or has no effect on tumor progression—have remained unclear. Our recent gene expression analyses have shown that SPARC is significantly downregulated in highly metastatic human prostate cancer cells. To test the role of endogenous SPARC in tumorigenesis directly, we examined cancer progression and metastasis in SPARC+/− and SPARC−/− mice using two separate transgenic mouse tumor models: transgenic adenocarcinoma of the mouse prostate (TRAMP) and murine mammary tumor virus-polyoma middle T (MMTV-PyMT). Surprisingly, in both instances, we found that loss of SPARC had no significant effects on tumor initiation, progression or metastasis. Tumor angiogenesis and collagen deposition were also largely unaffected. Our results indicate that, although differential SPARC expression may be a useful marker of aggressive, metastasis-prone tumors, loss of SPARC is not sufficient either to promote or to inhibit cancer progression in two spontaneous mouse tumor models.

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Abbreviations

SPARC:

Secreted protein, acidic and rich in cysteine

TRAMP:

Transgenic adenocarcinoma of the mouse prostate

MMTV-PyMT:

Murine mammary tumor virus-polyoma middle T

DL:

Dorsolateral prostate

VN:

Ventral prostate

SOI:

Surgical orthotopic implantation

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Acknowledgements

We are very grateful to Dr. E. Helene Sage and Sarah Funk (Benaroya Research Institute, Seattle, WA) for SPARC-deficient mice; Dr. Lei Xu (MIT) for MMTV-PyMT mice; Dr. Ailin Bai (MIT) for TRAMP mice; Jane Trevithick for technical assistance; and the MIT Division of Comparative Medicine for animal maintenance. This work was supported by grants from the NIH (RO1CA17007); from the Virginia and D. K. Ludwig Fund for Cancer Research; from the Prostate Cancer Foundation; from the National Cancer Institute’s Integrative Cancer Biology Program (U54-CA112967); and from the Howard Hughes Medical Institute, of which R. O. H. is an Investigator. S. Y. W. was further supported by an NIGMS Predoctoral Training Grant to the MIT Biology Department and by a David H. Koch Research Fellowship from the Center for Cancer Research.

Financial support

NIH (RO1CA17007); Virginia and D. K. Ludwig Fund for Cancer Research; Prostate Cancer Foundation; Integrative Cancer Biology Program (National Cancer Institute, U54-CA112967); Howard Hughes Medical Institute. S. Y. W. was further supported by an NIGMS Predoctoral Training Grant and by a David H. Koch Research Fellowship from the Center for Cancer Research.

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  1. Sunny Y. Wong

    Present address: University of California San Francisco, San Francisco, CA, 94158, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA

    Sunny Y. Wong, Denise Crowley & Richard O. Hynes

  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Sunny Y. Wong & Richard O. Hynes

  3. Department of Biomedical Sciences, Tufts School of Veterinary Medicine, North Grafton, MA, 01536, USA

    Roderick T. Bronson

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Correspondence to Richard O. Hynes.

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Wong, S.Y., Crowley, D., Bronson, R.T. et al. Analyses of the role of endogenous SPARC in mouse models of prostate and breast cancer. Clin Exp Metastasis 25, 109–118 (2008). https://doi.org/10.1007/s10585-007-9126-2

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  • DOI: https://doi.org/10.1007/s10585-007-9126-2

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