Systemic Par-4 inhibits non-autochthonous tumor growth

Yanming Zhao, Ravshan Burikhanov, Jason Brandon, Shirley Qiu, Brent J. Shelton, Brett Spear, Subbarao Bondada, Scott Bryson, Vivek M. Rangnekar

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 languageEnglish
Pages (from-to)152-157
Number of pages6
JournalCancer Biology and Therapy
Volume12
Issue number2
DOIs
StatePublished - 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

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