An ultra-metastatic model of human colon cancer in nude mice

Fang X. Sun, Aaron R Sasson, Ping Jiang, Zili An, Reza Gamagami, Lingna Li, A. R. Moossa, Robert M. Hoffman

Research output: Contribution to journalArticle

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Abstract

An ultra-high metastatic model of human colon cancer was developed in order to represent highly malignant patient disease for which there is no current model. Surgical orthotopic implantation (SOI) of a histologically intact liver metastasis fragment derived from a surgical specimen of a patient with metastatic colon cancer was initially implanted in the colon, liver and subcutaneously in nude mice. This tumor did not metastasize for the first 10 passages. At the eleventh passage, the tumor exhibited metastasis from the colon to the liver, spleen, and lymph nodes. At this time, two selective passages were carried out by transplanting resulting liver metastases in the nude mice to the colon of additional nude mice. After these two passages, the tumor became stably ultra-metastatic and was termed AC3488UM. One-hundred percent of mice transplanted with AC3488UM with SOI to the colon exhibited local growth, regional invasion, and spontaneous metastasis to the liver, lymph nodes, and spleen. While the maximum size of the primary tumor was 0.9 g, the metastatic liver was over 9 times the weight of the normal liver with the maximum weight of the metastatic liver over 12 g. Liver metastases were detected by the tenth day after transplantation in all animals. Half the animals died of metastatic tumor 25 days after transplantation. Histological characteristics of AC3488UM tumor were poorly differentiated adenocarcinoma of colon. Mutant p53 is expressed heterogeneously in the primary tumor and more homogeneously in the liver metastasis suggesting a possible role of p53 in the liver metastasis. The human origin of AC3488UM was confirmed by positive fluorescence staining for in situ hybridization of human DNA. The AC3488 human colon-tumor model with its ultra-high metastatic capability in each transplanted animal, short latency and a short median survival period is different from any known human colon cancer model and will be an important tool for the study of and development of new therapy for highly metastatic human colon cancer.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalClinical and Experimental Metastasis
Volume17
Issue number1
StatePublished - Jun 30 1999

Fingerprint

Nude Mice
Colonic Neoplasms
Liver
Colon
Neoplasm Metastasis
Neoplasms
Spleen
Transplantation
Lymph Nodes
Weights and Measures
Fluorescence In Situ Hybridization
Adenocarcinoma
Staining and Labeling
Survival
DNA

Keywords

  • Colon cancer
  • Liver metastatic model
  • Nude mice
  • Surgical orthotopic implantation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sun, F. X., Sasson, A. R., Jiang, P., An, Z., Gamagami, R., Li, L., ... Hoffman, R. M. (1999). An ultra-metastatic model of human colon cancer in nude mice. Clinical and Experimental Metastasis, 17(1), 41-48.

An ultra-metastatic model of human colon cancer in nude mice. / Sun, Fang X.; Sasson, Aaron R; Jiang, Ping; An, Zili; Gamagami, Reza; Li, Lingna; Moossa, A. R.; Hoffman, Robert M.

In: Clinical and Experimental Metastasis, Vol. 17, No. 1, 30.06.1999, p. 41-48.

Research output: Contribution to journalArticle

Sun, FX, Sasson, AR, Jiang, P, An, Z, Gamagami, R, Li, L, Moossa, AR & Hoffman, RM 1999, 'An ultra-metastatic model of human colon cancer in nude mice', Clinical and Experimental Metastasis, vol. 17, no. 1, pp. 41-48.
Sun FX, Sasson AR, Jiang P, An Z, Gamagami R, Li L et al. An ultra-metastatic model of human colon cancer in nude mice. Clinical and Experimental Metastasis. 1999 Jun 30;17(1):41-48.
Sun, Fang X. ; Sasson, Aaron R ; Jiang, Ping ; An, Zili ; Gamagami, Reza ; Li, Lingna ; Moossa, A. R. ; Hoffman, Robert M. / An ultra-metastatic model of human colon cancer in nude mice. In: Clinical and Experimental Metastasis. 1999 ; Vol. 17, No. 1. pp. 41-48.
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