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Cancer Biol Ther. 2011 Jul 15;12(2):152-7. Epub 2011 Jul 15.

Systemic Par-4 inhibits non-autochthonous tumor growth.

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1
Department of Radiation Medicine, University of Kentucky, Lexington, KY USA.

Abstract

The tumor suppressor protein Par-4 (Prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SAC domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SAC has not been validated in animal models. We show that Par-4/SAC-transgenic mice express systemic Par-4/SAC protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SAC pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SAC protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SAC is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.

PMID:
21613819
PMCID:
PMC3154287
[Indexed for MEDLINE]
Free PMC Article
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