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Trends in Cancer Research   Volumes    Volume 9 
Modulation of the opioid growth factor receptor alters the proliferation and progression of cancer
Nancy P. Kren, Ian S. Zagon, Patricia J. McLaughlin
Pages: 53 - 64
Number of pages: 12
Trends in Cancer Research
Volume 9 

Copyright © 2013 Research Trends. All rights reserved

The opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis is present and tonically active in neoplastic as well as non-neoplastic cells. Addition of exogenous OGF decreases cancer cell growth in vitro and represses tumor growth in nude mice. In the presence of OGF the OGFr translocates to the nucleus and delays the cell cycle at the G1/S phase by upregulating p16 and/or p21 cyclin-dependent inhibitory kinases. Transient knockdown of OGFr gene and protein in 31 different human cancer cell lines resulted in altered growth characteristics suggesting that the OGF-OGFr axis is ubiquitous in human cancer. Transient knockdown of the classical opioid receptors did not affect growth characteristics, and OGF has been shown to be the specific ligand for OGFr. Genetic manipulation of human cancer cell lines to stably overexpress the nuclear associated receptor OGFr extended doubling times in culture, and decreased tumor incidence and size in nude mice xenografted with transfected human pancreatic cancer cells, squamous carcinoma of the head and neck cells, or ovarian cancer cells, relative to wildtype cancer cells. OGFr has been detected in a variety of human biopsy samples from normal tissue, as well as from benign or malignant tumors. Genetic and protein analyses of biopsied tumor specimens, and control tissues, from patients with squamous cell carcinoma of the head and neck or ovarian cancer revealed a loss of OGFr protein and binding activity with advanced stages of cancer. OGFr mRNA levels were comparable in advanced head and neck tumors relative to normal or benign tissues suggesting that the receptor is modified during the progression of cancer. In colorectal cancer as well as pancreatic cancer it was demonstrated that the receptor is unaltered with tumor progression. The alterations or modifications to OGFr are unknown and may be specific for each type of cancer. This article will review our knowledge about how the OGF-OGFr axis is modulated in human cancer cell proliferation and tumor progression.
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