A primary tumor promotes dormancy of solitary tumor cells before inhibiting angiogenesis
| Autor: | M, Guba, G, Cernaianu, G, Koehl, E K, Geissler, K W, Jauch, M, Anthuber, W, Falk, M, Steinbauer |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Mice Inbred BALB C Time Factors Neovascularization Pathologic Recombinant Fusion Proteins Green Fluorescent Proteins Neoplasms Second Primary Mice SCID Neoplasms Experimental Immunohistochemistry Luminescent Proteins Mice Ki-67 Antigen Tumor Cells Cultured Animals Blood Vessels Neoplasm Metastasis |
| Zdroj: | Cancer research. 61(14) |
| ISSN: | 0008-5472 |
| Popis: | Mechanisms that regulate the transition of micrometastases from clinically undetectable and dormant to progressively growing are critically important but poorly understood in cancer biology. Here we examined the effect of a primary tumor on the growth of solitary tumor cells in the mouse liver, as well as on the development of tumor angiogenesis in a dorsal skin-fold chamber. s.c. placement of a CT-26 (BALB/c-derived mouse colon carcinoma) primary tumor markedly inhibited development of liver metastasis in BALB/c mice after subsequent intraportal injection of tumor cells. Dorsal skin-fold chamber experiments showed that this growth inhibition paralleled a strong antiangiogenic effect by the primary tumor. Furthermore, intravital microscopy of the liver after intraportal injection of green fluorescent protein-expressing tumor cells showed that primary tumors promoted dormancy of single tumor cells for up to 7 days. Immunohistological staining for Ki-67 confirmed that these solitary cells were indeed dormant. In contrast, in the absence of a primary tumor, GFP-expressing tumor cells quickly developed into micrometastases. Thus, primary CT-26 tumor implants nearly abrogated tumor metastasis by inhibition of angiogenesis and by promoting a state of single-cell dormancy. Knowledge of the mechanism underlying this dormancy state could result in the development of new therapeutic tools to fight cancer. |
| Databáze: | OpenAIRE |
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