A primary tumor promotes dormancy of solitary tumor cells before inhibiting angiogenesis

Guba, Markus and Cernaianu, Grigore and Koehl, Gudrun and Geissler, Edward K. and Jauch, Karl-Walter and Anthuber, Matthias and Falk, Werner and Steinbauer, Markus (2001) A primary tumor promotes dormancy of solitary tumor cells before inhibiting angiogenesis. CANCER RESEARCH, 61 (14). pp. 5575-5579. ISSN 0008-5472

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: GREEN FLUORESCENT PROTEIN; IN-VIVO VIDEOMICROSCOPY; METASTATIC INEFFICIENCY; HEMATOGENOUS METASTASIS; ENDOGENOUS INHIBITOR; CANCER-CELLS; ANGIOSTATIN; GROWTH; SUPPRESSION; MICE;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 21 Dec 2021 07:18
Last Modified: 21 Dec 2021 07:18
URI: https://pred.uni-regensburg.de/id/eprint/41259

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