Carboxypeptidase M (CPM - EC 22.214.171.124) is an extracellular peptidase attached to the outer membrane by a glycosyl-phosphatidylinositol (GPI) anchor. It cleaves C-terminal lysines and arginines from peptides and proteins. CPM’s localization in lipid rafts potentially links it with cell adhesion and signaling pathways.
A role in inflammation is supported by its regulated expression on macrophages and by the ability of CPM to inactivate anaphylatoxins and alter receptor specificity of bradykinin. We showed that CPM modulates the activity of chemokines CXCL12 and CCL1, providing further evidence for CPM’s involvement in inflammation, stem cell mobilization, monocyte recruitment and cancer (1-4).
In the cancer field, CPM attracted interest for two reasons. First, the CPM gene resides in an unstable region of chromosome 12 that is amplified in certain cancer types together with the known oncogene and cancer biomarker called MDM2. Second, CPM is abundantly expressed in tumor associated macrophages. We studied CPM in healthy kidney and renal cell carcinoma and found that it has potential as a biomarker for discrimination of cancer types and stratification of patients (1).
CPM expression is upregulated during mesenchymal stem cell differentiation, in particular during adipogenesis (4). Looking for a hypothesis on the function of CPM in adipogenesis or mature adipocytes, we searched the literature for potential CPM substrates among cytokines and hormones secreted by adipose tissue, also known as adipokines (2). To investigate whether CPM modulates the action of adipokines, we need to develop a selective CPM inhibitor.
1. Denis C J, Van Acker N, De Schepper S, De Bie M, Andries L, Fransen E, Hendriks D, Kockx MM, and Lambeir AM. Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma: Expression in Tumor-associated Neovasculature and Macrophages. J Histochem Cytochem, 2012 as doi:10.1369/0022155412470456.
2. Denis CJ, Deiteren K, Hendriks D, Proost P, Lambeir AM. Carboxypeptidase M in apoptosis, adipogenesis and cancer. Clin Chim Acta. 2012 as doi: 10.1016/j.cca.2012.11.012.
3. Denis C, Deiteren K, Mortier A, Tounsi A, Fransen E, Proost P, Renauld JC, Lambeir AM. C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity. PLoS One. 2012;7(3):e34199.
4. Marquez-Curtis L, Jalili A, Deiteren K, Shirvaikar N, Lambeir AM, Janowska-Wieczorek A. Carboxypeptidase M expressed by human bone marrow cells cleaves the C-terminal lysine of stromal cell-derived factor-1alpha: another player in hematopoietic stem/progenitor cell mobilization? Stem Cells. 2008;26:1211-20