Murine leukemia virus envelope gp70 is a shared biomarker for the high-sensitivity quantification of murine tumor burden

Abstract

The preclinical development of anticancer drugs including immunotherapeutics and targeted agents relies on the ability to detect minimal residual tumor burden as a measure of therapeutic efficacy. Real-time quantitative (qPCR) represents an exquisitely sensitive method to perform such an assessment. However, qPCR-based applications are limited by the availability of a genetic defect associated with each tumor model under investigation. Here, we describe an off-the-shelf qPCR-based approach to detect a broad array of commonly used preclinical murine tumor models. In particular, we report that the mRNA coding for the envelope glycoprotein 70 (gp70) encoded by the endogenous murine leukemia virus (MuLV) is universally expressed in 22 murine cancer cell lines of disparate histological origin but is silent in 20 out of 22 normal mouse tissues. Further, we detected the presence of as few as 100 tumor cells in whole lung extracts using qPCR specific for gp70, supporting the notion that this detection approach has a higher sensitivity as compared with traditional tissue histology methods. Although gp70 is expressed in a wide variety of tumor cell lines, it was absent in inflamed tissues, non-transformed cell lines, or pre-cancerous lesions. Having a high-sensitivity biomarker for the detection of a wide range of murine tumor cells that does not require additional genetic manipulations or the knowledge of specific genetic alterations present in a given neoplasm represents a unique experimental tool for investigating metastasis, assessing antitumor therapeutic interventions, and further determining tumor recurrence or minimal residual disease.

Keywords: :

• AH1
• gp70
• minimal residual disease
• MuLV
• retrovirus
• tumor-associated antigen

Citation: Scrimieri F, Askew D, Corn DJ, Eid S, Bobanga ID, Bjelac JA, Tsao ML, Allen F, Othman YS, Wang SG, et al. Murine leukemia virus envelope gp70 is a shared biomarker for the high-sensitivity quantification of murine tumor burden. OncoImmunology 2013; 2:e26889; 10.4161/onci.26889

Acknowledgments

The authors would like to acknowledge Deborah Sim Barkauskas for her technical help during the preparation of this manuscript, and the following people for their generous provision of tumor cell lines and tissue samples: Dr John Letterio, MD and Dr Sung-Hee Choi, PhD at Case Western Reserve University, Dr Greg Plautz, MD at The Cleveland Clinic, Dr TC Wu, MD, PhD. at Johns Hopkins University, and Dr Chand Khanna, DVM, PhD, Dr Crystal Mackall, MD and Dr Remis Orentis, PhD at The National Cancer Institute. The authors gratefully acknowledge the following funding support for this work: CWRU Orthopedics T32 (5T32AR7505–25 to FS), the National Cancer Institute (R01CA154656 to AYH; R01CA154656 S1 to FA), the St. Baldrick’s Foundation (AYH), the Cancer Research Institute (AYH), the Alex’s Lemonade Stand Foundation (AYH), the Gabrielle’s Angel Foundation (AYH), the Hyundai Hope-on-Wheels Program (AYH), the Steven G. AYA Foundation (AYH), the Rainbow Board of the Rainbow Babies and Children’s Hospital (IDB).

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.