Abstract 356: Photoacoustic imaging of pancreatic cancer proliferation via sigma-2 receptor/PGRMC1-eYFP

Sigma-2 receptor binding sites, recently identified as progesterone receptor membrane component 1 (PGRMC1) (Nature Communications, 2011; 2:380), are highly expressed in tumor cells. We have previously reported that measuring the sigma-2 receptor expression is a novel strategy for evaluating the proliferative status of tumors in vivo using the non-invasive imaging technique, positron emission tomography (PET). Our group has developed a series of sigma-2 receptor radioligands as PET imaging probes, one sigma-2 receptor radiotracer [18F]ISO-1 is under clinical evaluation for imaging the proliferation status in the patients with different types of cancers. PGRMC1 depleted human ovarian SKOV-3 cancer cells have been reported to lack tumor formation in mice and PGRMC1 depleted tumors displayed poor microvasculature system (Endocrinology, 2009; 150:4846-4854). To further understand the regulation of PGRMC1 in cell cycle and cancer proliferation, we have stably transfected PGRMC1-eYFP, enhanced yellow fluorescent protein conjugated PGRMC1, into human pancreatic BxPC3 cancer cells and those cells were transplanted into immunodeficient nude mice to grow into solid tumors; subsequently, a traditional fluorescence imaging system and an optical-resolution photoacoustic microscopy (OR-PAM) were utilized for in vivo monitoring of BxPC3 cancer cells growth and observing the surrounding microvasculature development for those tumors under conditions of sigma-2 receptor/PGRMC1 overexpression. Tumor tissue sections were prepared and in vitro fluorescence microscopy analysis of PGRMC1-eYFP cells revealed that PGRMC1-eYFP overexpressed cells form cluster patterns which may represent the proliferation priority created by PGRMC1 overexpression. The subcellular localization of PGRMC1-eYFP appeared to be similar to that of sigma-2 receptors reported previously by our group using the sigma-2 receptor fluorescent probes (Cancer Res 2007; 67, 6708-6716). PGRMC1-eYFP BxPC3 cells were surrounded by fully developed microvasculature system. Further application of this in vivo imaging platform for evaluating the sigma-2 receptor pharmacology and imaging proliferation is ongoing in our group. (Supported by CA 102869 and CA136398).Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 356. doi:1538-7445.AM2012-356

Duke Scholars

Author Junjie Yao Biomedical Engineering