title: Systemic Par-4 inhibits non-autochthonous tumor growth.
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.
authors: Department of Radiation Medicine, University of Kentucky, Lexington, KY USA.
authors: Yanming
authors: Y
authors: Zhao
authors: Ravshan
authors: R
authors: Burikhanov
authors: Jason
authors: J
authors: Brandon
authors: Shirley
authors: S
authors: Qiu
authors: Brent J
authors: BJ
authors: Shelton
authors: Brett
authors: B
authors: Spear
authors: Subbarao
authors: S
authors: Bondada
authors: Scott
authors: S
authors: Bryson
authors: Vivek M
authors: VM
authors: Rangnekar
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