This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guba, M. Articles by Steinbauer, M. Search for Related Content PubMed PubMed Citation Articles by Guba, M. Articles by Steinbauer, M.

A Primary Tumor Promotes Dormancy of Solitary Tumor Cells before Inhibiting Angiogenesis¹

Departments of Surgery [M. G., G. C., G. K., E. K. G., K-W. J., M. A., M. S.] and Internal Medicine I [W. F.], University of Regensburg, D-93042 Regensburg, Germany

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.

This article has been cited by other articles:

				R. Demicheli, M. W. Retsky, W. J. M. Hrushesky, M. Baum, and I. D. Gukas The effects of surgery on tumor growth: a century of investigations Ann. Onc., November 1, 2008; 19(11): 1821 - 1828. [Abstract] [Full Text] [PDF]

				D. Bakthavatsalam, D. A. Brock, N. N. Nikravan, K. D. Houston, R. D. Hatton, and R. H. Gomer The secreted Dictyostelium protein CfaD is a chalone J. Cell Sci., August 1, 2008; 121(15): 2473 - 2480. [Abstract] [Full Text] [PDF]

				D. A. Brock, W. N. van Egmond, Y. Shamoo, R. D. Hatton, and R. H. Gomer A 60-Kilodalton Protein Component of the Counting Factor Complex Regulates Group Size in Dictyostelium discoideum. Eukaryot. Cell, September 1, 2006; 5(9): 1532 - 1538. [Abstract] [Full Text] [PDF]

				S. Indraccolo, L. Stievano, S. Minuzzo, V. Tosello, G. Esposito, E. Piovan, R. Zamarchi, L. Chieco-Bianchi, and A. Amadori Interruption of tumor dormancy by a transient angiogenic burst within the tumor microenvironment. PNAS, March 14, 2006; 103(11): 4216 - 4221. [Abstract] [Full Text] [PDF]

				K. Tsuji, K. Yamauchi, M. Yang, P. Jiang, M. Bouvet, H. Endo, Y. Kanai, K. Yamashita, A. R. Moossa, and R. M. Hoffman Dual-Color Imaging of Nuclear-Cytoplasmic Dynamics, Viability, and Proliferation of Cancer Cells in the Portal Vein Area Cancer Res., January 1, 2006; 66(1): 303 - 306. [Abstract] [Full Text] [PDF]

				D. A. Brock and R. H. Gomer A secreted factor represses cell proliferation in Dictyostelium Development, October 15, 2005; 132(20): 4553 - 4562. [Abstract] [Full Text] [PDF]

				S. Chigurupati, T. Kulkarni, S. Thomas, and G. Shah Calcitonin Stimulates Multiple Stages of Angiogenesis by Directly Acting on Endothelial Cells Cancer Res., September 15, 2005; 65(18): 8519 - 8529. [Abstract] [Full Text] [PDF]

				R. Demicheli, R. Miceli, A. Moliterni, M. Zambetti, W. J. M. Hrushesky, M. W. Retsky, P. Valagussa, and G. Bonadonna Breast cancer recurrence dynamics following adjuvant CMF is consistent with tumor dormancy and mastectomy-driven acceleration of the metastatic process Ann. Onc., September 1, 2005; 16(9): 1449 - 1457. [Abstract] [Full Text] [PDF]

				A. Kolbinger, T. Gao, D. Brock, R. Ammann, A. Kisters, J. Kellermann, D. Hatton, R. H. Gomer, and B. Wetterauer A Cysteine-Rich Extracellular Protein Containing a PA14 Domain Mediates Quorum Sensing in Dictyostelium discoideum Eukaryot. Cell, June 1, 2005; 4(6): 991 - 998. [Abstract] [Full Text] [PDF]

				S. Meng, D. Tripathy, E. P. Frenkel, S. Shete, E. Z. Naftalis, J. F. Huth, P. D. Beitsch, M. Leitch, S. Hoover, D. Euhus, et al. Circulating Tumor Cells in Patients with Breast Cancer Dormancy Clin. Cancer Res., December 15, 2004; 10(24): 8152 - 8162. [Abstract] [Full Text] [PDF]

				S. Paris and R. Sesboue Metastasis models: the green fluorescent revolution? Carcinogenesis, December 1, 2004; 25(12): 2285 - 2292. [Abstract] [Full Text] [PDF]

				H.-K. Yu, J.-S. Kim, H.-J. Lee, J.-H. Ahn, S.-K. Lee, S.-W. Hong, and Y. Yoon Suppression of Colorectal Cancer Liver Metastasis and Extension of Survival by Expression of Apolipoprotein(a) Kringles Cancer Res., October 1, 2004; 64(19): 7092 - 7098. [Abstract] [Full Text] [PDF]

				C. J. Bruns, G. E. Koehl, M. Guba, M. Yezhelyev, M. Steinbauer, H. Seeliger, A. Schwend, A. Hoehn, K.-W. Jauch, and E. K. Geissler Rapamycin-Induced Endothelial Cell Death and Tumor Vessel Thrombosis Potentiate Cytotoxic Therapy against Pancreatic Cancer Clin. Cancer Res., March 15, 2004; 10(6): 2109 - 2119. [Abstract] [Full Text] [PDF]

				H. Seeliger, M. Guba, G. E. Koehl, A. Doenecke, M. Steinbauer, C. J. Bruns, C. Wagner, E. Frank, K.-W. Jauch, and E. K. Geissler Blockage of 2-Deoxy-D-Ribose-Induced Angiogenesis with Rapamycin Counteracts a Thymidine Phosphorylase-Based Escape Mechanism Available for Colon Cancer under 5-Fluorouracil Therapy Clin. Cancer Res., March 1, 2004; 10(5): 1843 - 1852. [Abstract] [Full Text] [PDF]

				J. A. Aguirre-Ghiso, Y. Estrada, D. Liu, and L. Ossowski ERKMAPK Activity as a Determinant of Tumor Growth and Dormancy; Regulation by p38SAPK Cancer Res., April 1, 2003; 63(7): 1684 - 1695. [Abstract] [Full Text] [PDF]

				M. Yang, E. Baranov, J.-W. Wang, P. Jiang, X. Wang, F.-X. Sun, M. Bouvet, A. R. Moossa, S. Penman, and R. M. Hoffman Direct external imaging of nascent cancer, tumor progression, angiogenesis, and metastasis on internal organs in the fluorescent orthotopic model PNAS, March 19, 2002; 99(6): 3824 - 3829. [Abstract] [Full Text] [PDF]