Real-Time GFP Intravital Imaging of the Difference in Cellular and Angiogenic Behavior of Subcutaneous and Orthotopic Nude-Mouse Models of Human PC-3 Prostate Cancer

There are two major types of mouse xenograft models of cancer: subcutaneous implantation and orthotopic implantation. Subcutaneous transplant models are widely used, with both cancer cell lines and human-tumor specimens.

Recently, subcutaneous models of patient tumors, termed patient-derived xenographs (PDX) have become highly popular and have acquired such names as "Avatar" and "Xenopatients". However, such s.c. models rarely metastasize and are therefore not patient-like. In contrast, orthotopic models have the capability to metastasize. If intact fragments of tumor tissue are implanted by surgical orthotopic implantation (SOI), the metastatic potential can match that of the donor patient. The present study images in real time, using green fluorescent protein (GFP) expression, the very different tumor behavior at the orthotopic and subcutaneous sites of human prostate cancer PC-3 in athymic nude mice. By day-2 after tumor implantation, the orthotopic tumor is already highly vascularized and the cancer cells have begun to migrate out of the tumor. In contrast, the subcutaneous tumor only begins to be vascularized by day-3 and cells do not migrate from the tumor. Angiogenesis is much more extensive in the orthotopic tumor throughout the two-week observation period. The orthotopic PC-3-GFP tumor progresses very rapidly and distinct metastasis have appeared in lymph nodes by day 3 which rapidly appear in many areas of the abdominal cavity including portal lymph nodes by day-7. At day-14, no invasion or metastasis was observed with the s.c. tumor even when the animal was extensively explored. This article is protected by copyright. All rights reserved.

Journal of cellular biochemistry. 2016 Mar 25 [Epub ahead of print]

Yong Zhang, Makoto Toneri, Huaiyu Ma, Zhijian Yang, Michael Bouvet, Yusuke Goto, Naohiko Seki, Robert M Hoffman

AntiCancer Inc., University of California San Diego, San Diego, CA., AntiCancer Inc., University of California San Diego, San Diego, CA., AntiCancer Inc., University of California San Diego, San Diego, CA., AntiCancer Inc., University of California San Diego, San Diego, CA., Department of Surgery, University of California San Diego, San Diego, CA., Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan., Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan., AntiCancer Inc., University of California San Diego, San Diego, CA.

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