Analyses of the role of endogenous SPARC in mouse models of prostate and breast cancer.
Document Type
Article
Publication Date
2008
Keywords
Animals, Antigens-Polyomavirus-Transforming, Breast-Neoplasms, Cell-Line-Tumor, Collagen, Crosses-Genetic, Mammary-Tumor-Virus-Mouse, Mice-Transgenic, Neoplasm-Metastasis, Neovascularization-Pathologic, Osteonectin, Prostatic-Neoplasms, Transplantation-Heterologous
First Page
109
Last Page
118
JAX Location
see Reprint Collection (a pdf is available)
JAX Source
Clin Exp Metastasis 2008; 25(2):109-18.
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.
Recommended Citation
Wong SY,
Crowley D,
Bronson RT,
Hynes RO.
Analyses of the role of endogenous SPARC in mouse models of prostate and breast cancer. Clin Exp Metastasis 2008; 25(2):109-18.