Opioid growth factor receptor is unaltered with the progression of human pancreatic and colon cancers

Abstract

Opioid growth factor (OGF) is an endogenous opioid peptide ([Met(5)]-enkephalin) that interacts with the OGF receptor (OGFr). OGF serves as a constitutively expressed and tonically active negative growth factor in neoplasia, and the OGF-OGFr axis contributes to the maintenance of an equilibrium in cell replication by targeting cyclin-dependent inhibitory kinase pathways. In a previous study, OGFr binding activity was found to decrease in concert with progression of human squamous cell carcinoma of the head and neck (SCCHN). To investigate the relationship of OGFr to advancement of human pancreatic and colon cancers, tumor cells were transplanted into nude mice, and small, medium, and large neoplasias were assessed for OGFr number and affinity by receptor binding analysis, and for gene expression of OGFr mRNA by Northern blot analysis. In addition, OGF levels were monitored in plasma. OGFr binding affinity and capacity, as well as transcriptional activity of OGFr, were not influenced by the size or state of differentiation of pancreatic or colon tumors. Plasma levels of OGF were 3.5- to 7.9-fold less in animals with pancreatic or colon cancers than in nude mice not receiving xenografts, and no differences in OGF values were recorded between small and large tumors. These data on human pancreatic and colon cancers, along with information in earlier studies on SCCHN, indicate that alterations in the OGF receptor are dependent on tumor type and that the integrity of the OGF-OGFr axis insofar as tumorigenesis needs to be evaluated for each type of neoplasm. This information will be relevant in the design of therapeutic modalities, the diagnosis and prognosis of neoplasia, as well as understanding of the processes and mechanisms of carcinogenesis.