CD13/Aminopeptidase N in Tumor Growth and Angiogenesis

Petrović, Nenad; Schacke, Wolfgang; Shapiro, Linda H.

doi:10.1007/978-1-4419-8869-0_9

Cited by 11 publications

(14 citation statements)

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“…The role of APN activity in cancer has classically been linked to tumor progression, angiogenesis, and invasiveness (29,31,34). However, our observations suggest a role linked to an additional factor other than progression, as in CCRCC APN activity, is strongly suppressed in cancer tissue but not in the normal tissue surrounding tumors.…”

Section: Discussioncontrasting

confidence: 70%

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Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma

Varona¹,

Blanco²,

López³

et al. 2007

American Journal of Physiology-Renal Physiology

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Peptides play important roles in cell regulation and signaling in many tissues and are regulated by peptidases, most of which are highly expressed in the kidney. Several peptide convertases have a function in different tumor stages, and some have been clearly characterized as diagnostic and prognostic markers for solid tumors, including renal cancer; however, little is known about their in vivo role in kidney tumors. The present study compares the activity of a range of peptidases in human tumor samples and nontumor tissue obtained from clear cell renal cell carcinoma (CCRCC) patients. To cover the complete spectrum and subcellular distribution of peptide-converting activity, acid, neutral, basic, and omega activities were selected. CCRCC displays a selective and restricted pattern of peptidase activities. Puromycin-sensitive aminopeptidase activity in the tumor increases [tumor (t) = 10,775 vs. nontumor (n) = 7,635 units of peptidase (UP)/mg protein; P < 0.05], whereas aminopeptidase N decreases (t = 6,664 vs. n = 33,381 UP/mg protein; P < 0.001). Aminopeptidase B activity of the particulate fraction in tumors decreases (t = 2,399 vs. n = 13,536 UP/mg protein; P < 0.001) compared with nontumor tissues, and aspartyl-aminopeptidase activity decreases significantly in CCRCC (t = 137 vs. n = 223 UP/mg protein; P < 0.05). Soluble and particulate pyroglutamyl peptidase I activities, aminopeptidase A activity, and soluble aminopeptidase B activity do not vary in renal cancer. The relative expression for the aforementioned peptidases, assayed using quantitative RT-PCR, increases in CCRCC for aminopeptidases B (1.5-fold) and A (19-fold), aspartyl-aminopeptidase (3.9-fold), puromycin-sensitive aminopeptidase (2.5-fold), and pyroglutamyl peptidase I (7.6-fold). Only aminopeptidase N expression decreases in tumors (1.3-fold). This peptidase activity profile in the neoplastic kidney suggests a specific role for the studied convertases and the possible involvement of an intracrine renin-angiotensin system in the pathogenesis of CCRCC.

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Section: Discussioncontrasting

confidence: 70%

“…Among the factors involved in the etiopathogenesis of CCRCC, a major point of interest in cancer research concerns proteases, which are involved in metastasis (31), and particularly peptidases, which would appear to play a role, not only in metastatic processes but also in tumor cell growth and differentiation-related pathways (8,36).…”

Section: Discussionmentioning

confidence: 99%

Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma

Varona¹,

Blanco²,

López³

et al. 2007

American Journal of Physiology-Renal Physiology

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“…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%

“…For example, inhibitors of the APN and APB, such as bestatin and puromycin, have been reported to induce apoptosis onset in solid tumors (12,30,31). Moreover, decreases of mRNA for APN cause inhibition of angiogenesis (16), and APA appears to promote tumor angiogenesis (25).…”

Section: Discussionmentioning

confidence: 99%

“…Among the multiple factors involved in neoplastic transformation and tumor progression, peptidases appear to play a pivotal role. These enzymes are known to have functions in growth control, differentiation, and the signal transduction of many cell systems by modulating the activity of bioactive peptides, and several cell surface peptidases have been characterized as solid tumor markers with different diagnostic and prognostic rates (17,30). Renal parenchyma is a tissue very rich in both soluble and particulate peptidases (24,31).…”

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confidence: 99%

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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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Increased APN/CD13 and acid aminopeptidase activities in head and neck squamous cell carcinoma

et al. 2009

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CD13/Aminopeptidase N in Tumor Growth and Angiogenesis

Abstract: The CD13/am inopeptidase N cell surface peptidase was originall y identified as a marker for tumors of the hematopoietic system. Recent evidence howe ver extends the role ofCDI3/APN to solid tumors as well where it is postulated to regulate angiogenes is and tumor metastasis.

Cited by 11 publications

References 100 publications

Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma

Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma

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

Increased APN/CD13 and acid aminopeptidase activities in head and neck squamous cell carcinoma

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