Arginyl Aminopeptidase

Cadel, Sandrine; Piesse, Christophe; Gouzy-Darmon, Cécile; Cohen, Paul A.; Foulon, Thierry

doi:10.1007/978-1-4419-8869-0_6

Cited by 2 publications

(2 citation statements)

References 55 publications

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“…Moreover, immunohistochemistry assays reported that APA is practically absent from the cell surface in oncocytic cells, whereas, although there is a decrease in staining with respect to normal renal cells, this enzyme is strongly expressed in CCRCC (28). As cell surface APN, APB, and APA were found to be altered in a tumor type-specific way, our results are consistent with other studies that involve the aforementioned particulate forms in specific roles in renal cancer (9,10,20,29).…”

Section: Discussionsupporting

confidence: 92%

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Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma

Blanco

Larrinaga²,

Perez³

et al. 2008

American Journal of Physiology-Renal Physiology

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Renal cell carcinomas (RCCs) are neoplasias with high prevalence and mortality. We previously reported that several peptidases may be involved in the pathophysiology of clear cell renal cell carcinoma (CCRCC). Now, to gain insight into the reasons that lead the various RCC types to behave very differently with regard to aggressiveness and response to anticancer treatments, we analyzed subsets of chromophobe renal cell carcinoma (ChRCC), and renal oncocytoma (RO), a benign tumor; as well as different grades and stages of CCRCCs. Particulate APN, APB, and APA activities were decreased in both ChRCC and RO (tumor vs. nontumor tissues). Interestingly, activities were downregulated in a tumor-type specific way and the intensities of the decreases were stronger in the benign tumor than in the malignant type. Moreover, when two key histopathological parameters for tumor prognosis (high vs. low stage and grade) were analyzed, increases of activity were also observed in several of these cell surface peptidases (APN, APB). Some soluble activities (APB, Asp-AP) were also downregulated in the RCCs. With respect to genetic expression, PSA and APN were in a positive correlation related to their activities in both ChRCC and RO; but not APB, Asp-AP, APA, and PGI. These results may suggest an involvement of several peptidases in the pathophysiology of renal cancer, since they presented different patterns of activity and expression in tumors with different behaviors. peptide signaling; renal tumor behavior; chromophobe carcinoma; renal oncocytoma RENAL CELL CARCINOMAS (RCCs) are neoplasias with high prevalence and mortality rates. One of the more difficult challenges in treating RCCs involves identifying and distinguishing aggressive tumors from those likely to remain indolent with little detriment to the patient. The clear cell type of carcinoma (CCRCC) is by far the most frequent histological subtype of RCC, accounting for 70% of cases (27), a prevalence rate that explains its intrinsic clinical interest. However, not all kidney tumors are the same and the different histological subtypes of RCC behave quite differently, both with regard to aggressiveness in the patient and response to treatment (3,22). For example, when CCRCC is localized, prognosis after surgery is good, but patients with spread CCRCC have a decidedly worse prognosis (3). The chromophobe subtype of RCC (ChRCC) is much less frequent (5% of cases) than CCRCC. On the other hand, the renal oncocytoma (RO) is also a relatively uncommon entity, accounting for only 5% of cases of renal tumors (1). With respect to its clinical interest, ChRCC differs from CCRCC in its lower rate of metastasis. As a result, surgical removal of localized or even locally advanced disease is usually associated with a better prognosis (1, 3). Moreover, although ChRCC and RO are thought to share a common lineage (1), ChRCC is malignant and RO is benign. As a consequence, a deeper understanding of the molecular mechanisms underlying these different renal tumors could be helpful in gaining in...

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Section: Discussionsupporting

confidence: 92%

“…Most evidences are related to APN (9,12,14,16,18,23,30,31). Although not as frequent as for APN, there is also evidence of the involvement of APA (18,35,25) and APB (31,32) in cancer pathobiology.…”

Section: Discussionmentioning

confidence: 99%

Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma

Blanco

Larrinaga²,

Perez³

et al. 2008

American Journal of Physiology-Renal Physiology

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The impact of peptidase activity on clear cell renal cell carcinoma survival

Larrinaga

Blanco

Sanz

et al. 2012

American Journal of Physiology-Renal Physiology

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Several studies have proposed that protease expression and activity may have a predictive value in the survival of clear cell renal cell carcinoma (CCRCC). Most efforts on this issue have been focused on the analysis of matrix metalloproteinases (MMP) and very little on the role of other proteases, such as peptidases. The catalytic activity of 9 peptidases (APN, APB, ASP, CAP, DPP-IV, NEP/CD10, PEP, PGI, and PSA) was quantified by fluorometric methods in a series of 79 CCRCC patients, and the results obtained were analyzed for survival (Kaplan-Meier curves, log-rank test, and Cox multivariate analysis). CCRCC patients with higher activity levels of membrane-bound APN and soluble APN, DPP-IV, and CAP had significantly shorter 5-yr survival rates than those with lower levels. By contrast, higher soluble APB activity significantly correlated with longer survival. Our data suggest the involvement of peptidases in the biological aggressiveness of CCRCC and support the usefulness of measuring these proteases to assess the prognosis of patients with CCRCC.

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Arginyl Aminopeptidase

Cited by 2 publications

References 55 publications

Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma

Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma

The impact of peptidase activity on clear cell renal cell carcinoma survival

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