Elucidation of molecules that control cancer cell growth and invasion will greatly facilitate the identification of biomarkers that can predict impending tumor metastasis, as well as provide targets for therapy. Currently, numerous biomarkers, some associated with metastasis, have been reported to be useful in identifying aggressive tumors and predicting prognosis. Despite the huge repertoire of biomarkers reported, there is still a lack of reliable markers for predicting future metastasis from biopsies or resected primary tumors for most cancers. Recently, we have found a molecule, carboxypeptidase E (CPE), also known as carboxypeptidase H which levels are correlated with growth and metastasis in a variety of human cancer cell lines. We showed by Western blot that the human neuroblastoma cell line, IMR-32 that has been amplified with MYCN and is highly metastatic, overexpressed CPE compared to the matched cell line SK-NAS which has low metastasic potential. Likewise, in a variety of human tumor cell lines from liver, colon, breast, prostate, colon, head and neck, elevated expression of CPE was also observed in cell lines that are highly metastatic, compared to the matched tumor lines that have low metastatic potential. In addition, we have shown that in mouse pheochromocytoma cell lines, one with high metastatic potential (MTT cells) had higher levels of CPE than one with low metastatic potential (MPC cells). ? ? We also demonstrated that CPE plays a role in promoting growth and cell invasion in human cancer cells. When highly metastatic human cell lines from breast (MDA-MB-23), prostate (DU145), head and neck (MDA 1986), colon (HT29) and liver (MHCC97M3), were down-regulated in CPE expression by si-RNA by 60-85%, the si-CPE treated cells showed a 52-85% inhibition of growth. The matrigel invasion assay was used to assess invasion capability of the tumor cell lines transduced with CPE si-RNA. In all the tumor lines, suppression of CPE expression led to 70-85% inhibition of invasion. Thus CPE plays a role in promoting growth and invasion in multiple types of cancer cell lines.
