Biochemical, Structural and Pathophysiological Aspects of Prorenin and (Pro)renin Receptor

Nabi, A.H.M. Nurun; Suzuki, Fujio

doi:10.5772/38553

Cited by 1 publication

(1 citation statement)

References 187 publications

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“…Structural analysis revealed that (P)RR comprises a signal peptide, an extracellular domain, a single transmembrane domain, and a short cytoplasmic domain (7). Since the discovery of (P)RR by Nguyen and colleagues (6), a large number of studies have demonstrated that (P)RR also has renin-angiotensin system-independent functions, especially in activation of signal transduction pathways (8). Recent findings have revealed that (P)RR is an integral component of canonical and noncanonical Wnt receptor complexes and is involved in early embryonic development (9,10).…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Effects of Monoclonal Antibodies against (Pro)Renin Receptor in Pancreatic Ductal Adenocarcinoma

Rahman

Matsuyama

Ebihara

et al. 2020

Molecular Cancer Therapeutics

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We previously reported that silencing of the PRR gene, which encodes the (pro)renin receptor [(P)RR], significantly reduced Wnt/b-catenin-dependent development of pancreatic ductal adenocarcinoma (PDAC). Here, we examined the effects of a panel of blocking mAbs directed against the (P)RR extracellular domain on proliferation of the human PDAC cell lines PK-1 and PANC-1 in vitro and in vivo. We observed that four rat anti-(P) RR mAbs induced accumulation of cells in the G 0 -G 1 -phase of the cell cycle and significantly reduced proliferation in vitro concomitant with an attenuation of Wnt/b-catenin signaling. Systemic administration of the anti-(P)RR mAbs to nude mice bearing subcutaneous PK-1 xenografts significantly decreased tumor expression of active b-catenin and the proliferation marker Ki-67, and reduced tumor growth. In contrast, treatment with the handle region peptide of (pro)renin did not inhibit tumor growth in vitro or in vivo, indicating that the effects of the anti-(P)RR mAbs were independent of the reninangiotensin system. These data indicate that mAbs against human (P)RR can suppress PDAC cell proliferation by hindering activation of the Wnt/b-catenin signaling pathway. Thus, mAb-mediated (P)RR blockade could be an attractive therapeutic strategy for PDAC.

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