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 SA C domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SA C has not been validated in animal models. We show that Par-4/SA C-transgenic mice express systemic Par-4/SA C protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SA C 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 SA C protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SA C is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.
Original language | English |
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Pages (from-to) | 152-157 |
Number of pages | 6 |
Journal | Cancer Biology and Therapy |
Volume | 12 |
Issue number | 2 |
DOIs | |
State | Published - Jul 15 2011 |
Bibliographical note
Funding Information:This study was supported by KLCR grant, NIH/ NCI grants CA060872, CA105453 and CA116658 (to V.M.R.).
Keywords
- Metastasis
- Par-4
- Systemic protein
ASJC Scopus subject areas
- Molecular Medicine
- Oncology
- Pharmacology
- Cancer Research