title: Real-Time GFP Intravital Imaging of the Differences in Cellular and Angiogenic Behavior of Subcutaneous and Orthotopic Nude-Mouse Models of Human PC-3 Prostate Cancer.
abstract: 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 2-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. These results explain why orthotopic tumors mimimc clinical metastatic tumors in nude mice and why subcutaneous tumors do not. J. Cell. Biochem. 117: 2546-2551, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: AntiCancer Inc., San Diego, California.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: AntiCancer Inc., San Diego, California.|Department of Surgery, University of California San Diego, San Diego, California.
authors.forename: Makoto
authors.initials: M
authors.lastname: Toneri
authors.affiliation: AntiCancer Inc., San Diego, California.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Ma
authors.affiliation: AntiCancer Inc., San Diego, California.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan. naoseki@faculty.chiba-u.jp.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.affiliation: AntiCancer Inc., San Diego, California. all@anticancer.com.|Department of Surgery, University of California San Diego, San Diego, California. all@anticancer.com.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007279:Injections, Subcutaneous; D000069416:Intravital Microscopy / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D049452:Green Fluorescent Proteins
keywords: ANGIOGENESIS; GFP IMAGING; INTRAVITAL; INVASION; METASTASIS; ORTHOTOPIC; PC-3; PROSTATE CANCER; SUBCUTANEOUS