Abstract
BackgroundThe development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease.MethodsWe injected immunoincompetent nude mice intraportally with different numbers (1 × 105, 1 × 106 and 5 × 106 cells) of the human colon carcinoma cell lines HT-29 and SW-620 and investigated by histological studies and CK-20 RT-PCR the occurrence of hematogenous metastases and the dissemination of human tumor cells in bone marrow.ResultsOnly the injection of 1 × 106 cells of each colon carcinoma cell line produced acceptable perioperative mortality with reproducible induction of hepatic metastases in up to 89% of all animals. The injection of 1 × 106 cells also generated tumor cell dissemination in the bone marrow in up to 63% of animals with hepatic metastases.ConclusionThe present intraportal injection model in immunoincompetent nude mice represents a biologically relevant and adequate animal model for the induction of both reproducible hepatic metastasis and tumor cell dissemination in the bone marrow as a sign of MRD.
Highlights
The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease
The classical view is that metastatic spread is a late process in malignant progression, but recent work suggested that dissemination of primary cancer cells to distant sites like the bone marrow might be an early event [5]
In the group injected with 1 × 106 tumor cells, MRD was found in about 60% of all animals with evident metastases
Summary
The development of new therapeutic strategies for treatment of metastasized colorectal carcinoma requires biologically relevant and adequate animal models that generate both reproducible metastasis and the dissemination of tumor cells in the form of so-called minimal residual disease (MRD), an expression of the systemic character of neoplastic disease. Colorectal carcinoma constitutes approximately 15% of all cases of cancer and is one of the most common malignant diseases worldwide. Metastases of colorectal carcinomas are initially localized in the liver in 40% to 80% of patients. The principal curative treatment option is surgical resection, only one fourth of patients with liver metastases are operable [2]. Following initial radical curative surgery, metastases are attributed to the dissemination of tumor cells in the form of minimal residual disease (MRD), whose prognostic relevance continues to be discussed [3,4]. The classical view is that metastatic spread is a late process in malignant progression, but recent work suggested that dissemination of primary cancer cells to distant sites like the bone marrow might be an early event [5]
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