This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Friedl, P. Articles by Zänker, K. S. Search for Related Content PubMed PubMed Citation Articles by Friedl, P. Articles by Zänker, K. S.

Migration of Coordinated Cell Clusters in Mesenchymal and Epithelial Cancer Explants in Vitro¹

Institute of Immunology, University of Witten/Herdecke, Stockumer Strasse 10, 58448 Witten, Germany [P. F., K. S. Z.]; Departments of Oral Biology [P. F., P. B. N., K. S. Z.] and Anatomy and Cell Biology [P. A. W., D. W. L.], McGill University; Departments of Pathology [P. J. C.] and Surgery [R. J. T.], Montreal General Hospital; and Department of Otolaryngology, Jewish General Hospital [M. B.], Montreal, Canada

The invasion and migration occurring in primary neoplastic tissue explants were studied by using a three-dimensional collagen matrix model, subsequent time-lapse videomicroscopy, and computer-assisted cell tracking. We show that not only single cells but groups of clustered cells comprising 5 to more than 100 cells detach from the primary tumor lesion and migrate within the adjacent extracellular matrix. These clusters were highly polarized, resulting in a high directional persistence of migration. Locomoting cell clusters were observed in primary cultures from invasive oral squamous cell carcinomas (6 of 9), ductal breast carcinomas (2 of 3), and rhabdomyosarcoma (1 of 1), whereas normal oral mucosa (0 of 4) was cell cluster negative. Thus, locomoting cell clusters could be a novel and potentially important mechanism of cancer cell invasion and metastasis.

¹ Supported by Fritz-Bender-Foundation, Munich, Germany. Because the dynamics of the behavior of locomotiong cell clusters described in this manuscript are insufficiently documented by static images alone, essential key sequences of the source tapes have been accepted by Spektrum der Wissenschaft, the German edition of Scientific American, for publication as video documentation (ISBN 3-86025-801-X). An English version of this video production is in preparation.

² To whom requests for reprints should be addressed.

Received 7/17/95. Accepted 8/28/95.

This article has been cited by other articles:

				N. Kumar, R. Afeyan, H.-D. Kim, and D. A. Lauffenburger Multipathway Model Enables Prediction of Kinase Inhibitor Cross-Talk Effects on Migration of Her2-Overexpressing Mammary Epithelial Cells Mol. Pharmacol., June 1, 2008; 73(6): 1668 - 1678. [Abstract] [Full Text] [PDF]

				J. Wels, R. N. Kaplan, S. Rafii, and D. Lyden Migratory neighbors and distant invaders: tumor-associated niche cells Genes & Dev., March 1, 2008; 22(5): 559 - 574. [Abstract] [Full Text] [PDF]

				T. R. Geiger and D. S. Peeper Critical Role for TrkB Kinase Function in Anoikis Suppression, Tumorigenesis, and Metastasis Cancer Res., July 1, 2007; 67(13): 6221 - 6229. [Abstract] [Full Text] [PDF]

				J. J. Christiansen and A. K. Rajasekaran Reassessing Epithelial to Mesenchymal Transition as a Prerequisite for Carcinoma Invasion and Metastasis. Cancer Res., September 1, 2006; 66(17): 8319 - 8326. [Abstract] [Full Text] [PDF]

				N. Kumar, M. H. Zaman, H.-D. Kim, and D. A. Lauffenburger A High-Throughput Migration Assay Reveals HER2-Mediated Cell Migration Arising from Increased Directional Persistence Biophys. J., August 15, 2006; 91(4): L32 - L34. [Abstract] [Full Text] [PDF]

				D. H. Geho, R. W. Bandle, T. Clair, and L. A. Liotta Physiological Mechanisms of Tumor-Cell Invasion and Migration Physiology, June 1, 2005; 20(3): 194 - 200. [Abstract] [Full Text] [PDF]

				P. Szafranski and S. Goode A Fasciclin 2 morphogenetic switch organizes epithelial cell cluster polarity and motility Development, May 1, 2004; 131(9): 2023 - 2036. [Abstract] [Full Text] [PDF]

				Y. Hegerfeldt, M. Tusch, E.-B. Brocker, and P. Friedl Collective Cell Movement in Primary Melanoma Explants: Plasticity of Cell-Cell Interaction, {beta}1-Integrin Function, and Migration Strategies Cancer Res., April 1, 2002; 62(7): 2125 - 2130. [Abstract] [Full Text] [PDF]

				P. Friedl, S. Borgmann, and E.-B. Brocker Amoeboid leukocyte crawling through extracellular matrix: lessons from the Dictyostelium paradigm of cell movement J. Leukoc. Biol., October 1, 2001; 70(4): 491 - 509. [Abstract] [Full Text] [PDF]

				K. Masur, K. Lang, B. Niggemann, K. S. Zanker, and F. Entschladen High PKC {alpha} and Low E-Cadherin Expression Contribute to High Migratory Activity of Colon Carcinoma Cells Mol. Biol. Cell, July 1, 2001; 12(7): 1973 - 1982. [Abstract] [Full Text] [PDF]

				K. Nabeshima, T. Inoue, Y. Shimao, Y. Okada, Y. Itoh, M. Seiki, and M. Koono Front-Cell-specific Expression of Membrane-Type 1 Matrix Metalloproteinase and Gelatinase A during Cohort Migration of Colon Carcinoma Cells Induced by Hepatocyte Growth Factor/Scatter Factor Cancer Res., July 1, 2000; 60(13): 3364 - 3369. [Abstract] [Full Text]

				A. Roetger, A. Merschjann, T. Dittmar, C. Jackisch, A. Barnekow, and B. Brandt Selection of Potentially Metastatic Subpopulations Expressing c-erbB-2 from Breast Cancer Tissue by Use of an Extravasation Model Am. J. Pathol., December 1, 1998; 153(6): 1797 - 1806. [Abstract] [Full Text] [PDF]