This Article 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 Farina, K. L. Articles by Jones, J. G. Search for Related Content PubMed PubMed Citation Articles by Farina, K. L. Articles by Jones, J. G.

Cell Motility of Tumor Cells Visualized in Living Intact Primary Tumors Using Green Fluorescent Protein¹

Departments of Anatomy and Structural Biology [K. L. F., J. B. W., J. R., H. L., J. E. S., J. S. C.] and Pathology [J. G. J.], Albert Einstein College of Medicine, Bronx, New York 10461

Metastasis is the leading cause of death in cancer patients. Cell motility is believed to be a necessary step in the metastatic process (L. Liotta and W. G. Stetler-Stevenson, In: Cancer: Principles and Practice of Oncology, pp. 134–149, 1993). Currently, most methods available to study the behavior of metastatic tumor cells are indirect, e.g., cell motility is examined in vitro and the results are correlated with metastatic capability (A. W. Partin, et al., Cancer Treat. Res., 59: 121–130, 1992). We have developed a model that directly examines the motility of metastatic primary tumor cells in situ. A metastatic rat breast cancer cell line was established that constitutively expresses green fluorescent protein. Upon s.c. injection of these cells into the mammary fat pad of female Fischer 344 rats, primary and metastatic tumors form that fluoresce when they are excited with FITC-filtered light. Animations of metastatic tumor cells moving in live rats were generated by intravital imaging of the primary tumor in situ on a laser scanning confocal microscope. With this model, the behavioral phenotype of metastatic and nonmetastatic tumor cells can be described and determined. This information will allow the effects of genetic manipulations or therapeutic treatments on this phenotype to be determined (D. R. Soll, Int. Rev. Cytol, 163: 43–104, 1995). This is the first time that living primary tumor cells in a live animal have been visualized as part of a clinically relevant model.

¹ This work was supported by grants from the NIH and the Department of Defense Army Breast Cancer Program. The data in this paper will be submitted in partial fulfillment of the requirement for the Degree of Doctor of Philosophy in the Sue Golding Graduate Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University, New York, NY (K. L. F.).

² Present address: Department of Medicine/Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461.

³ To whom requests for reprints should be addressed, at Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-4068; Fax: (718) 430-8996; E-mail: condeeli@aecom.yu.edu.

Received 2/12/98. Accepted 4/29/98.

This article has been cited by other articles:

				M. Parri, M. L. Taddei, F. Bianchini, L. Calorini, and P. Chiarugi EphA2 Reexpression Prompts Invasion of Melanoma Cells Shifting from Mesenchymal to Amoeboid-like Motility Style Cancer Res., March 1, 2009; 69(5): 2072 - 2081. [Abstract] [Full Text] [PDF]

				J. B. Wyckoff, Y. Wang, E. Y. Lin, J.-f. Li, S. Goswami, E. R. Stanley, J. E. Segall, J. W. Pollard, and J. Condeelis Direct Visualization of Macrophage-Assisted Tumor Cell Intravasation in Mammary Tumors Cancer Res., March 15, 2007; 67(6): 2649 - 2656. [Abstract] [Full Text] [PDF]

				K. Yamauchi, M. Yang, P. Jiang, M. Xu, N. Yamamoto, H. Tsuchiya, K. Tomita, A. R. Moossa, M. Bouvet, and R. M. Hoffman Development of Real-time Subcellular Dynamic Multicolor Imaging of Cancer-Cell Trafficking in Live Mice with a Variable-Magnification Whole-Mouse Imaging System. Cancer Res., April 15, 2006; 66(8): 4208 - 4214. [Abstract] [Full Text] [PDF]

				L. Xu and X. Deng Tobacco-specific Nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Phosphorylation of {micro}- and m-Calpain in Association with Increased Secretion, Cell Migration, and Invasion J. Biol. Chem., December 17, 2004; 279(51): 53683 - 53690. [Abstract] [Full Text] [PDF]

				W. Wang, S. Goswami, K. Lapidus, A. L. Wells, J. B. Wyckoff, E. Sahai, R. H. Singer, J. E. Segall, and J. S. Condeelis Identification and Testing of a Gene Expression Signature of Invasive Carcinoma Cells within Primary Mammary Tumors Cancer Res., December 1, 2004; 64(23): 8585 - 8594. [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]

				J. Wyckoff, W. Wang, E. Y. Lin, Y. Wang, F. Pixley, E. R. Stanley, T. Graf, J. W. Pollard, J. Segall, and J. Condeelis A Paracrine Loop between Tumor Cells and Macrophages Is Required for Tumor Cell Migration in Mammary Tumors Cancer Res., October 1, 2004; 64(19): 7022 - 7029. [Abstract] [Full Text] [PDF]

				A. Mamoune, J.-H. Luo, D. A. Lauffenburger, and A. Wells Calpain-2 as a Target for Limiting Prostate Cancer Invasion Cancer Res., August 1, 2003; 63(15): 4632 - 4640. [Abstract] [Full Text] [PDF]

				C. M. John, H. Leffler, B. Kahl-Knutsson, I. Svensson, and G. A. Jarvis Truncated Galectin-3 Inhibits Tumor Growth and Metastasis in Orthotopic Nude Mouse Model of Human Breast Cancer Clin. Cancer Res., June 1, 2003; 9(6): 2374 - 2383. [Abstract] [Full Text] [PDF]

				W. Wang, J. B. Wyckoff, V. C. Frohlich, Y. Oleynikov, S. Huttelmaier, J. Zavadil, L. Cermak, E. P. Bottinger, R. H. Singer, J. G. White, et al. Single Cell Behavior in Metastatic Primary Mammary Tumors Correlated with Gene Expression Patterns Revealed by Molecular Profiling Cancer Res., November 1, 2002; 62(21): 6278 - 6288. [Abstract] [Full Text] [PDF]

				S. C. Tucker and A. Casadevall Replication of Cryptococcus neoformans in macrophages is accompanied by phagosomal permeabilization and accumulation of vesicles containing polysaccharide in the cytoplasm PNAS, March 5, 2002; 99(5): 3165 - 3170. [Abstract] [Full Text] [PDF]

				C. W. Wong, A. Lee, L. Shientag, J. Yu, Y. Dong, G. Kao, A. B. Al-Mehdi, E. J. Bernhard, and R. J. Muschel Apoptosis: An Early Event in Metastatic Inefficiency Cancer Res., January 1, 2001; 61(1): 333 - 338. [Abstract] [Full Text]

				J. B. Wyckoff, J. E. Segall, and J. S. Condeelis The Collection of the Motile Population of Cells from a Living Tumor Cancer Res., October 1, 2000; 60(19): 5401 - 5404. [Abstract] [Full Text]

				J. B. Wyckoff, J. G. Jones, J. S. Condeelis, and J. E. Segall A Critical Step in Metastasis: In Vivo Analysis of Intravasation at the Primary Tumor Cancer Res., May 1, 2000; 60(9): 2504 - 2511. [Abstract] [Full Text]

				E. A. Shestakova, J. Wyckoff, J. Jones, R. H. Singer, and J. Condeelis Correlation of {beta}-Actin Messenger RNA Localization with Metastatic Potential in Rat Adenocarcinoma Cell Lines Cancer Res., March 1, 1999; 59(6): 1202 - 1205. [Abstract] [Full Text] [PDF]

				G. Naumov, S. Wilson, I. MacDonald, E. Schmidt, V. Morris, A. Groom, R. Hoffman, and A. Chambers Cellular expression of green fluorescent protein, coupled with high-resolution in vivo videomicroscopy, to monitor steps in tumor metastasis J. Cell Sci., January 6, 1999; 112(12): 1835 - 1842. [Abstract] [PDF]