Abstract 5586: <i>In vitro</i> investigation of the proliferative and metastatic role of CD13 in cancer

CD13 (Aminopeptidase N,APN) is a glycosylated ectopeptidase with diverse physiological functions including proliferation, differentiation, migration and angiogenesis1. CD13 is a marker for neoangiogenesis that is detected in tumor neovasculature, but not in the normal vasculature, contributing with tumor growth, invasion, and metastasis. In vitro studies have revealed association between CD13 various cancer types including human glioblastoma2 and prostate3 cancers. Thus, CD13 is an appealing target for the delivery of drugs in CD13-expressing tumors which can reduce tumor growth and progression. An example is the aminopeptidase inhibitor, Ubenimex (Bestatin), which has been approved in Japan as an adjuvant to chemotherapy for acute non-lymphocytic leukemia. However, the overlapping substrate specificity of the aminopeptidase family of proteins leads to the challenge of developing a specific CD13 inhibitor. Prostate cancer (PC) and neuroblastoma (NB) are both highly malignant tumors that can spread into the bone marrow, liver, lymph nodes and bones. The effect of CD13 inhibition by Ubenimex in PC cells has previously been investigated with results showing decrease of cell growth in vitro and in vivo, however, this was only shown in two PC cell lines, LNCaP and PC-33. Hence, we are expanding this study into additional PC cell lines. Meanwhile, 70% of NB patients demonstrate a metastatic profile and there is currently no evidence yet of a link between NB to CD13. Given that CD13 is a regulator of tumor invasion, investigating the significance of CD13 in PC and NB can deepen our understating in its role in cell proliferation, migration, and metastasis. CD13 protein expression in PC and NB tumor xenografts and cell lines were investigated using western blot analysis, with differential expression identified between the cell lines. The importance of CD13 protein expression status will be reported; cell lines were treated with CD13 inhibitors including bestatin and actinonin, with evaluation of cell proliferation and migration using functional assays (MTT and scratch assays respectively). These data provide evidence towards the importance of CD13 in PC and NB, which will facilitate the development of a novel targeted therapy for CD13-expressing tumors that reduces the toxicity of traditional chemotherapy. 1.Lendeckel U, Karimi F, Al Abdulla R, Wolke C. The Role of the Ectopeptidase APN/CD13 in Cancer. Biomedicines. 2023;11(3).2.Zhang W, Blank A, Kremenetskaia I, Nitzsche A, Acker G, Vajkoczy P, et al. CD13 expression affects glioma patient survival and influences key functions of human glioblastoma cell lines in vitro. BMC Cancer. 2024;24(1):369.3.Wang X, Niu Z, Jia Y, Cui M, Han L, Zhang Y, et al. Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells. Oncol Rep. 2016;35(4):2121-30. Citation Format: April J. Baral, Gabriel C. Nwokolo, Sarah Mcgowan, Steven D. Shnyder, Robert A. Falconer. In vitro investigation of the proliferative and metastatic role of CD13 in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5586.