RESUMEN

INTRODUCTION: In the recent literature, carboxypeptidase M (CPM) emerged as a potential cancer biomarker. CPM modulates receptor signaling of kinins, anaphylatoxins, and chemokines. These CPM substrates affect proliferation, angiogenesis, and apoptosis of cancer cells. What is the evidence that CPM is a drug target for cancer therapy? AREAS COVERED: The literature was searched using PubMed with the search terms "carboxypeptidase M" and/or "chromosome 12q13-15" eventually combined with general terms related to cancer. Information was retrieved from the GEO database and material of gene expression and proteomic studies. EXPERT OPINION: CPM is a part of the molecular signature of many cancers. There is good evidence that it is useful for the discrimination and stratification of cancer types, possibly in combination with other markers such as EGFR and MDM2. Whether it is also a drug target remains to be determined. Lung, kidney, brain, and the reproductive system contain relatively high levels of CPM, but its functions in those tissues are largely unknown. CPM is expressed on tumor-associated macrophages. To facilitate the investigation of CPM in tumor-associated inflammation and in the other aspects of tumor biology, it is necessary to develop potent and selective CPM inhibitors.

Asunto(s)

Biomarcadores de Tumor , Metaloendopeptidasas/metabolismo , Neoplasias/enzimología , Animales , Proliferación Celular , Proteínas Ligadas a GPI/metabolismo , Humanos , Neoplasias/patología , Neovascularización Patológica

RESUMEN

Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman's basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney.

Asunto(s)

Carcinoma de Células Renales/enzimología , Neoplasias Renales/enzimología , Riñón/enzimología , Riñón/patología , Macrófagos/enzimología , Metaloendopeptidasas/análisis , Adulto , Carcinoma de Células Renales/irrigación sanguínea , Carcinoma de Células Renales/patología , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/patología , Receptores ErbB/análisis , Proteínas Ligadas a GPI/análisis , Humanos , Inmunohistoquímica , Riñón/irrigación sanguínea , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/patología , Macrófagos/patología , Persona de Mediana Edad , Neovascularización Patológica/enzimología , Neovascularización Patológica/patología , Análisis de Matrices Tisulares

RESUMEN

This review covers carboxypeptidase M (CPM) research that appeared in the literature since 2009. The focus is on aspects that are new or interesting from a clinical perspective. Available research tools are discussed as well as their pitfalls and limitations. Evidence is provided to suggest the potential involvement of CPM in apoptosis, adipogenesis and cancer. This evidence derives from the expression pattern of CPM and its putative substrates in cells and tissues. In recent years CPM emerged as a potential cancer biomarker, in well differentiated liposarcoma where the CPM gene is co-amplified with the oncogene MDM2; and in lung adenocarcinoma where coexpression with EGFR correlates with poor prognosis. The available data call for extended investigation of the function of CPM in tumor cells, tumor-associated macrophages, stromal cells and tumor neovascularisation. Such experiments could be instrumental to validate CPM as a therapeutic target.

Asunto(s)

Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/enzimología , Biomarcadores de Tumor/metabolismo , Liposarcoma/irrigación sanguínea , Liposarcoma/enzimología , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/enzimología , Metaloendopeptidasas/metabolismo , Neoplasias de los Tejidos Blandos/irrigación sanguínea , Neoplasias de los Tejidos Blandos/enzimología , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma del Pulmón , Adipogénesis/genética , Apoptosis/genética , Biomarcadores de Tumor/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Expresión Génica , Humanos , Liposarcoma/diagnóstico , Liposarcoma/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Metaloendopeptidasas/genética , Neovascularización Patológica , Pronóstico , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Transducción de Señal , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Especificidad por Sustrato