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U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

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Cancer Res 2008 Nov 15;68(22):9311-7

Human Adrenomedullin Up-regulates Interleukin-13 Receptor {alpha}2 Chain in Prostate Cancer In vitro and In vivo: A Novel Approach to Sensitize Prostate Cancer to Anticancer Therapy.

Joshi BH, Leland P, Calvo A, Green JE, Puri RK


Interleukin-13 (IL-13) receptor alpha2 (IL-13Ralpha2), a high-affinity IL-13 binding subunit and a tumor antigen, is amplified in a variety of human tumor cell lines and tumors in vivo. By cDNA microarray, we have shown that gene transfer of human and rat adrenomedullin (AM) up-regulates IL-13Ralpha2 in a human prostate tumor cell line. Here, we show that IL-13Ralpha2 mRNA and protein are also up-regulated in PC-3 prostate tumor cells by recombinant AM (rAM) and human synthetic AM peptide in a dose-dependent manner in vitro and in vivo in mouse prostate tumor model. The 8- to 10-fold up-regulation of IL-13Ralpha2 by rAM or AM peptide in prostate tumor cells in vitro and in vivo increased their sensitivity to IL-13PE cytotoxin consisting of IL-13 and a truncated form of Pseudomonas exotoxin. Immunodeficient mice with established prostate tumors transfected with AM or treated with AM peptide showed reduction in tumor size by intratumoral administration of IL-13PE in a dose-dependent manner. At the highest dose (three 100 mug/kg/d every alternate day), >70% reduction of tumor size was observed compared with controls (P

Category: Journal Article
PubMed ID: #19010904 DOI: 10.1158/0008-5472
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29