RETRACTED ARTICLE: Carboxypeptidase E: Elevated Expression Correlated with Tumor Growth and Metastasis in Pheochromocytomas and Other Cancers

Abstract

SummaryExpression of carboxypeptidase E, a prohormone processing enzyme in different cancer types was analyzed from data in the GEO profile database, and experimentally in pheochromocytomas. Microarray data from the GEO profile database indicated that significantly elevated levels of CPE mRNA was found in many non-endocrine cancers: cervical, colon rectal, renal cancers, Ewing sarcomas (bone cancer) and various types of astrocytomas and oligodendrogliomas, but expression of CPE mRNA was virtually absent in their respective counterpart normal tissues. Moreover there was a good correlation of high CPE mRNA expression with metastasis in cervical cancer and anaplastic oligodendrogliomas and neoplastic astrocytomas. Elevated CPE mRNA expression was found in neuroendocrine tumors in lung and pituitary adenomas, although the significance is unclear since endocrine and neuroendocrine cells normally express CPE. However studies of a neuroendocrine tumor, pheochromocytoma, revealed expression of not only wild type CPE, but a variant which was correlated with tumor behavior. Extremely high CPE mRNA copy numbers of the variant were found in very large or invasive tumors, both of which usually indicate poor prognosis. Thus, all the data suggest that CPE is involved in tumorogenesis and that it may play a role in promoting tumor growth and invasion. CPE could potentially serve as a diagnostic and prognostic biomarker for different cancer types.

Carboxypeptidase E promotes cancer cell survival, but inhibits migration and invasion

“…It functions by entering the nucleus where it is involved in the activation of a metastatic gene, Nedd9 , and possibly others [11]. Unlike CPE- N, CPE appears to be expressed only in endocrine and neuroendocrine tumors and in glioblastomas [6; 10]. Until recently, it was presumed that CPE expressed in these tumors function within secretory granules in the cell as an enzyme that processes immature hormone intermediates to mature peptide hormones and neuropeptides which are synthesized in abundance in these tumors [22; 23; 24].…”

“…High throughput microarray studies have correlated elevated CPE mRNA levels with metastasis in a number of non-endocrine cancers [10], although the form of CPE protein translated from these mRNAs was not analyzed. Recently, an N-terminally truncated splice isoform of CPE, known as CPE- N was identified and shown to be a molecule that induces tumor metastasis [11].…”

The “go or grow” potential of gliomas is linked to the neuropeptide processing enzyme carboxypeptidase E and mediated by metabolic stress

“…1a) [30], the fact that CPE mRNA expression was significantly reduced in glioblastomas as compared to normal brain tissue in the TCGA and REMBRANDT databases (Fig. 1b), the function of CPE as a peptidase [7] and the knowledge from the literature that low CPE expression is correlated with tumor malignancy in neuroendocrine tumors [11,12,22] prompted us to analyze whether CPE is involved in glioma malignancy and progression. We found reduced CPE protein and mRNA expression levels especially in gliomas both in vivo and in vitro (Figs.…”

Molecular targeted therapies in adrenal, pituitary and parathyroid malignancies

“…Other agents Carboxypeptidase E (CPE) is a prehormone-processing enzyme expressed in different types of cancer including NETs, mainly of the lung and pituitary (Murthy et al 2010). Extremely high CPE mRNA copy numbers of the N-terminal splice isoform variant were found in various human metastatic tumour cell lines, including metastatic PCs.…”