title: A primary tumor promotes dormancy of solitary tumor cells before inhibiting angiogenesis.
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.
authors.affiliation: Department of Surgery, University of Regensburg, D-93042 Regensburg, Germany. markus.guba@klinik.uni-regensburg.de
authors.forename: M
authors.initials: M
authors.lastname: Guba
authors.forename: G
authors.initials: G
authors.lastname: Cernaianu
authors.forename: G
authors.initials: G
authors.lastname: Koehl
authors.forename: E K
authors.initials: EK
authors.lastname: Geissler
authors.forename: K W
authors.initials: KW
authors.lastname: Jauch
authors.forename: M
authors.initials: M
authors.lastname: Anthuber
authors.forename: W
authors.initials: W
authors.lastname: Falk
authors.forename: M
authors.initials: M
authors.lastname: Steinbauer
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D019394:Ki-67 Antigen; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins