HUMAN VILLOUS ADENOMAS ENGRAFTED INTO ACID MICE SURVIVE FOR PROLONGED PERIOD WITHOUT MALIGNANT TRANSFORMATION

被引:5
作者
BUMPERS, HL
ALOSCO, TR
WANG, HQ
PETRELLI, NJ
HOOVER, EL
BANKERT, RB
机构
[1] ROSWELL PK CANC INST, DEPT SURG ONCOL, BUFFALO, NY 14215 USA
[2] ROSWELL PK CANC INST, DEPT MOLEC IMMUNOL, BUFFALO, NY 14215 USA
关键词
COLON TUMOR; POLYP; POLYPOSIS COLI; TUMORIGENESIS; CARCINOGENESIS;
D O I
10.1172/JCI117572
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Human villous adenomas are thought to represent premalignancies that subsequently give rise to colorectal adenocarcinomas. Currently there is no in vivo model in which to study the dedifferentiation and malignant transformation of these tumors. We establish here that human villous adenomas can be successfully engrafted into severe combined immunodeficient (scid) mice. Furthermore, these xenografts remain viable for up to 18 mo after either a subcutaneous or intraperitoneal inoculation of the human tissue. Tumors grew slowly and secreted a clear mucinous fluid. Examination of the tumors histologically at 1, 4, and 12 mo after implantation revealed that the villous polypoid structure was maintained and islands of atypical cells were observed within pockets of mucin surrounding the adenomatous tissue. No gross or histologic evidence of malignancy was detected throughout the 20-mo observation period. The human identity of the cells in the graft was confirmed by DNA in situ hybridization with a human-specific probe. We conclude that the human-scid xenograft described here represents a viable animal model with which to study the potential malignant dedifferentiation of villous adenomas over a prolonged period of time and to evaluate the possible contribution of selected oncogenic vectors on the malignant transformation of these adenomas.
引用
收藏
页码:2153 / 2157
页数:5
相关论文
共 12 条
[1]  
BANKERT RB, 1989, CURR TOP MICROBIOL, V152, P201
[2]   A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS [J].
FEARON, ER ;
VOGELSTEIN, B .
CELL, 1990, 61 (05) :759-767
[3]  
FRESHNEY RI, 1983, MANUAL BASIC TECHNIQ, P295
[4]   A COMPARISON OF METHODS FOR THE DETECTION OF HUMAN PAPILLOMAVIRUS DNA BY INSITU HYBRIDIZATION WITH BIOTINYLATED PROBES ON HUMAN CARCINOMA CELL-LINES - APPLICATION TO WART SECTIONS [J].
GUERINREVERCHON, I ;
CHARDONNET, Y ;
CHIGNOL, MC ;
THIVOLET, J .
JOURNAL OF IMMUNOLOGICAL METHODS, 1989, 123 (02) :167-176
[5]   THE SCID-HU MOUSE - MURINE MODEL FOR THE ANALYSIS OF HUMAN HEMATOLYMPHOID DIFFERENTIATION AND FUNCTION [J].
MCCUNE, JM ;
NAMIKAWA, R ;
KANESHIMA, H ;
SHULTZ, LD ;
LIEBERMAN, M ;
WEISSMAN, IL .
SCIENCE, 1988, 241 (4873) :1632-1639
[6]   TRANSFER OF A FUNCTIONAL HUMAN IMMUNE-SYSTEM TO MICE WITH SEVERE COMBINED IMMUNODEFICIENCY [J].
MOSIER, DE ;
GULIZIA, RJ ;
BAIRD, SM ;
WILSON, DB .
NATURE, 1988, 335 (6187) :256-259
[7]   POTENTIAL OF THE SCID MOUSE AS A HOST FOR HUMAN TUMORS [J].
MUELLER, BM ;
REISFELD, RA .
CANCER AND METASTASIS REVIEWS, 1991, 10 (03) :193-200
[8]   EVOLUTION OF CANCER OF COLON AND RECTUM [J].
MUTO, T ;
BUSSEY, HJR ;
MORSON, BC .
CANCER, 1975, 36 (06) :2251-2270
[9]  
PARASKEVA C, 1990, ANTICANCER RES, V10, P1189
[10]   GENETIC ALTERATIONS DURING COLORECTAL-TUMOR DEVELOPMENT [J].
VOGELSTEIN, B ;
FEARON, ER ;
HAMILTON, SR ;
KERN, SE ;
PREISINGER, AC ;
LEPPERT, M ;
NAKAMURA, Y ;
WHITE, R ;
SMITS, AMM ;
BOS, JL .
NEW ENGLAND JOURNAL OF MEDICINE, 1988, 319 (09) :525-532