Orthotopic microinjection of human colon cancer cells in nude mice induces tumor foci in all clinically relevant metastatic sites

被引:189
作者
Virtudes Cespedes, Maria
Espina, Carolina
Angel Garcia-Cabezas, Miguel
Trias, Manuel
Boluda, Alicia
Gomez del Pulgar, Maria Teresa
Josep Sancho, Francesc
Nistal, Manuel
Carlos Lacal, Juan
Mangues, Ramon
机构
[1] Hosp Santa Creu & Sant Pau, Lab Invest Gastrointestinal, Inst Recerca, Barcelona 08025, Spain
[2] Hosp Santa Creu & Sant Pau, Grp Oncogenesi & Antitumorals, Barcelona 08025, Spain
[3] Hosp Santa Creu & Sant Pau, Dept Surg, Barcelona 08025, Spain
[4] Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain
[5] Inst Invest Biomed, Alberto Sols Lab 1 10, Madrid, Spain
[6] Hosp Univ La Paz, Dept Pathol, Madrid, Spain
关键词
D O I
10.2353/ajpath.2007.060773
中图分类号
R36 [病理学];
学科分类号
100104 [病理学与病理生理学];
摘要
Despite metastasis as an important cause of death in colorectal cancer patients, current animal models of this; disease are scarcely metastatic. We evaluated whether direct orthotopic cell microinjection, between the mucosa and the muscularis layers of the cecal wall of nude mice, drives tumor foci to the most relevant metastatic sites observed in humans and/or improves its yield as compared with previous methods. We injected eight animals each tested human colorectal cancer cell line (HCT-116, SW-620, and DLD-1), using a especially designed micropipette under binocular guidance, and evaluated the take rate, local growth, pattern and rate of dissemination, and survival time. Take rates were in the 75 to 88% range. Tumors showed varying degrees of mesenteric and retroperitoneal lymphatic foci (57 to 100%), hematogenous dissemination to liver (29 to 67%) and lung (29 to 100%), and peritoneal carcinomatosis (29 to 100%). Tumor staging closely correlated with animal survival. Therefore, the orthotopic cell microinjection procedure induces tumor foci in the most clinically relevant metastatic sites: colon-draining lymphatics, liver, lung, and peritoneum. The replication of the clinical pattern of dissemination makes it a good model for advanced colorectal cancer. Moreover, this procedure also enhances the rates of hematogenous and lymphatic dissemination at relevant sites, as compared with previously described methods that only partially reproduce this pattern.
引用
收藏
页码:1077 / 1085
页数:9
相关论文
共 60 条
[1]
Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor [J].
An, ZL ;
Wang, XE ;
Willmott, N ;
Chander, SK ;
Tickle, S ;
Docherty, AJP ;
Mountain, A ;
Millican, AT ;
Morphy, R ;
Porter, JR ;
Epemolu, RO ;
Kubota, T ;
Moossa, AR ;
Hoffman, RM .
CLINICAL & EXPERIMENTAL METASTASIS, 1997, 15 (02) :184-195
[2]
BRESALIER RS, 1990, CANCER RES, V50, P1299
[3]
Metastasis of human colon cancer is altered by modifying expression of the β-galactoside-binding protein galectin 3 [J].
Bresalier, RS ;
Mazurek, N ;
Sternberg, LR ;
Byrd, JC ;
Yunker, CK ;
Nangia-Makker, P ;
Raz, A .
GASTROENTEROLOGY, 1998, 115 (02) :287-296
[4]
BRESALIER RS, 1987, CANCER RES, V47, P1398
[5]
BRESALIER RS, 1995, CANCER RES, V55, P2476
[6]
Dissemination and growth of cancer cells in metastatic sites [J].
Chambers, AF ;
Groom, AC ;
MacDonald, IC .
NATURE REVIEWS CANCER, 2002, 2 (08) :563-572
[7]
Increased plasma MMP9 in integrin α1-null mice enhances lung metastasis of colon carcinoma cells [J].
Chen, XW ;
Su, Y ;
Fingleton, B ;
Acuff, H ;
Matrisian, LM ;
Zent, R ;
Pozzi, A .
INTERNATIONAL JOURNAL OF CANCER, 2005, 116 (01) :52-61
[8]
Corpet DE, 2003, CANCER EPIDEM BIOMAR, V12, P391
[9]
DEVITA VTJ, 2005, CANC PRINCIPLES PRAC
[10]
MICE DEFICIENT FOR P53 ARE DEVELOPMENTALLY NORMAL BUT SUSCEPTIBLE TO SPONTANEOUS TUMORS [J].
DONEHOWER, LA ;
HARVEY, M ;
SLAGLE, BL ;
MCARTHUR, MJ ;
MONTGOMERY, CA ;
BUTEL, JS ;
BRADLEY, A .
NATURE, 1992, 356 (6366) :215-221