Jeremy R Jackson1, Youngleem Kim1, Robert C Seeger2, Eugene S Kim3. 1. Division of Pediatric Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA. 2. Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA. 3. Division of Pediatric Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA. Electronic address: eugeneskim@chla.usc.edu.
Abstract
INTRODUCTION: Patients with high-risk neuroblastoma rarely succumb to their primary tumor but rather from relapsed metastatic disease after surgery. We, therefore, sought to create an in vivo model of minimal residual disease (MRD), which clinically replicates tumor recurrence and metastasis after surgical resection. METHODS: Neuroblastoma cell lines CHLA-255, CHLA-136, and SH-SY5Y were used. After establishing orthotopic xenografts, mice were divided into control tumor group (sham operation at 14days) and tumor resection group (resection at 14days). Mice were monitored by bioluminescent imaging and sacrificed when institutional criteria for euthanasia were met. RESULTS: In the CHLA-255 and CHLA-136 cell lines, mice experienced significantly longer survival following tumor resection (p<0.007). There was no survival benefit seen in the SH-SY5Y cell line (p=0.29). Bioluminescent imaging demonstrated metastatic disease in 100% of all tumor resection mice and varying rates of metastasis in control mice (4 of 5 CHLA-255, 2 of 4 CHLA-136, and 7 of 7 SH-SY5Y). CONCLUSION: In this study, we describe a novel neuroblastoma model of MRD in mice. This MRD model serves as an innovative means to test preclinical therapies as well as elucidate mechanisms of metastatic disease in experimental neuroblastoma.
INTRODUCTION: Patients with high-risk neuroblastoma rarely succumb to their primary tumor but rather from relapsed metastatic disease after surgery. We, therefore, sought to create an in vivo model of minimal residual disease (MRD), which clinically replicates tumor recurrence and metastasis after surgical resection. METHODS: Neuroblastoma cell lines CHLA-255, CHLA-136, and SH-SY5Y were used. After establishing orthotopic xenografts, mice were divided into control tumor group (sham operation at 14days) and tumor resection group (resection at 14days). Mice were monitored by bioluminescent imaging and sacrificed when institutional criteria for euthanasia were met. RESULTS: In the CHLA-255 and CHLA-136 cell lines, mice experienced significantly longer survival following tumor resection (p<0.007). There was no survival benefit seen in the SH-SY5Y cell line (p=0.29). Bioluminescent imaging demonstrated metastatic disease in 100% of all tumor resection mice and varying rates of metastasis in control mice (4 of 5 CHLA-255, 2 of 4 CHLA-136, and 7 of 7 SH-SY5Y). CONCLUSION: In this study, we describe a novel neuroblastoma model of MRD in mice. This MRD model serves as an innovative means to test preclinical therapies as well as elucidate mechanisms of metastatic disease in experimental neuroblastoma.
Authors: Tal Teitz; Jennifer J Stanke; Sara Federico; Cori L Bradley; Rachel Brennan; Jiakun Zhang; Melissa D Johnson; Jan Sedlacik; Madoka Inoue; Ziwei M Zhang; Sharon Frase; Jerold E Rehg; Claudia M Hillenbrand; David Finkelstein; Christopher Calabrese; Michael A Dyer; Jill M Lahti Journal: PLoS One Date: 2011-04-29 Impact factor: 3.240