| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
University of Texas Health Science Center, Department of Medicine, Division of Endocrinology and Metabolism, San Antonio, Texas 78284-7877 [G. M., C. R. D., P. J. W., G. R. M., T. Y.], and Department of Oral and Maxillofacial Surgery II, Okayama University School of Dentistry, Okayama 700, Japan [A. S.]
The molecular mechanisms by which human cancer cells spread to bone are largely unexplored. The process likely involves cell adhesion molecules (CAMs) that are responsible for homophilic and heterophilic cell-cell interactions. One relevant CAM may be the calcium-dependent transmembrane glycoprotein E-cadherin. To investigate the involvement of E-cadherin in breast cancer metastasis to bone, we used an in vivo model in which osteolytic bone metastases preferentially occur after injections of cancer cells directly into the arterial circulation through the left ventricle of the hearts of nude mice. We have found that E-cadherinnegative human breast cancer cells MDA-MB-231 (MDA-231) develop radiographically detectable multiple osteolytic bone metastases and cachexia in this model. However, MDA-231 breast cancer cells that were transfected with E-cadherin cDNA showed a dramatically impaired capacity to form osteolytic metastases and induce cachexia. Histological and histomorphometrical analyses of bones of mice bearing mock-transfected MDA-231 revealed aggressive metastatic tumor, whereas metastatic tumor burden was significantly decreased in the bones of mice bearing E-cadherin-expressing MDA-231. Nude mice bearing E-cadherin-transfected MDA-231 breast cancer cells survived longer than mice bearing mock-transfected MDA-231 breast cancer cells. Anchorage-dependent and -independent growth in culture and tumor enlargement in the mammary fat pad of nude mice were unchanged between mock-transfected and E-cadherin-expressing MDA-231, suggesting that these differences in metastatic behavior are not due to an impairment of cell growth and tumorigenicity. Our results show the suppressive effects of E-cadherin expression on bone metastasis by circulating breast cancer cells and suggest that the modulation of expression of this CAM may reduce the destructive effects of breast cancer cells on bone.
1 Supported by NIH Grants PO1-CA40035, CA58183 (Specialized Program of Research Excellence), and CA63628.
2 To whom requests for reprints should be addressed, at Department of Medicine/Endocrinology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7877. Phone: (210) 567-4900; Fax: (210) 567-6693; E-mail: yoneda@uthscsa.edu
Received 4/22/96. Accepted 7/ 2/96.
This article has been cited by other articles:
|
|
 |
|
  M. A. Smit, T. R. Geiger, J.-Y. Song, I. Gitelman, and D. S. Peeper A Twist-Snail Axis Critical for TrkB-Induced Epithelial-Mesenchymal Transition-Like Transformation, Anoikis Resistance, and Metastasis Mol. Cell. Biol., July 1, 2009; 29(13): 3722 - 3737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Strube, J. Hoffmann, E. Stepina, P. Hauff, U. Klar, and S.-M. Kakonen Sagopilone Inhibits Breast Cancer Bone Metastasis and Bone Destruction Due to Simultaneous Inhibition of Both Tumor Growth and Bone Resorption Clin. Cancer Res., June 1, 2009; 15(11): 3751 - 3759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shen, D. S. Hirsch, C. A. Sasiela, and W. J. Wu Cdc42 Regulates E-cadherin Ubiquitination and Degradation through an Epidermal Growth Factor Receptor to Src-mediated Pathway J. Biol. Chem., February 22, 2008; 283(8): 5127 - 5137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mauro, S. Catalano, G. Bossi, M. Pellegrino, I. Barone, S. Morales, C. Giordano, V. Bartella, I. Casaburi, and S. Ando Evidences that Leptin Up-regulates E-Cadherin Expression in Breast Cancer: Effects on Tumor Growth and Progression Cancer Res., April 1, 2007; 67(7): 3412 - 3421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G A Clines and T A Guise Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone Endocr. Relat. Cancer, September 1, 2005; 12(3): 549 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shinozaki, D. S.B. Hoon, A. E. Giuliano, N. M. Hansen, H.-J. Wang, R. Turner, and B. Taback Distinct Hypermethylation Profile of Primary Breast Cancer Is Associated with Sentinel Lymph Node Metastasis Clin. Cancer Res., March 15, 2005; 11(6): 2156 - 2162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. K. Mell, J. J. Meyer, M. Tretiakova, A. Khramtsov, C. Gong, S. D. Yamada, A. G. Montag, and A. J. Mundt Prognostic Significance of E-Cadherin Protein Expression in Pathological Stage I-III Endometrial Cancer Clin. Cancer Res., August 15, 2004; 10(16): 5546 - 5553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, J. Backer, A. S. K. Wong, E. L. Schwanke, B. G. Stewart, and M. Pasdar Bcl-2 expression decreases cadherin-mediated cell-cell adhesion J. Cell Sci., September 15, 2003; 116(18): 3687 - 3700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Myoui, R. Nishimura, P. J. Williams, T. Hiraga, D. Tamura, T. Michigami, G. R. Mundy, and T. Yoneda C-Src Tyrosine Kinase Activity Is Associated with Tumor Colonization in Bone and Lung in an Animal Model of Human Breast Cancer Metastasis Cancer Res., August 15, 2003; 63(16): 5028 - 5033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Wang, R. K. Hansen, D. Radisky, T. Yoneda, M. H. Barcellos-Hoff, O. W. Petersen, E. A. Turley, and M. J. Bissell Phenotypic Reversion or Death of Cancer Cells by Altering Signaling Pathways in Three-Dimensional Contexts J Natl Cancer Inst, October 2, 2002; 94(19): 1494 - 1503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Winding, R. NicAmhlaoibh, H. Misander, P. Hoegh-Andersen, T. L. Andersen, C. Holst-Hansen, A.-M. Heegaard, N. T. Foged, N. Brunner, and J.-M. Delaisse Synthetic Matrix Metalloproteinase Inhibitors Inhibit Growth of Established Breast Cancer Osteolytic Lesions and Prolong Survival in Mice Clin. Cancer Res., June 1, 2002; 8(6): 1932 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yi, P. J. Williams, M. Niewolna, Y. Wang, and T. Yoneda Tumor-derived Platelet-derived Growth Factor-BB Plays a Critical Role in Osteosclerotic Bone Metastasis in an Animal Model of Human Breast Cancer Cancer Res., February 1, 2002; 62(3): 917 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mauro, M. Bartucci, C. Morelli, S. Ando', and E. Surmacz IGF-I Receptor-induced Cell-Cell Adhesion of MCF-7 Breast Cancer Cells Requires the Expression of Junction Protein ZO-1 J. Biol. Chem., October 19, 2001; 276(43): 39892 - 39897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, M. Tondravi, J. Liu, E. Smith, C. C. Haudenschild, M. Kaczmarek, and X. Zhan Cortactin Potentiates Bone Metastasis of Breast Cancer Cells Cancer Res., September 1, 2001; 61(18): 6906 - 6911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhong, Y. Delgado, J. Gomez, S. W. Lee, and R. Perez-Soler Loss of H-Cadherin Protein Expression in Human Non-Small Cell Lung Cancer Is Associated with Tumorigenicity Clin. Cancer Res., June 1, 2001; 7(6): 1683 - 1687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, C.-l. Huang, K. Kameyama, E. Hayashi, A. Yamauchi, S. Kobayashi, and H. Yokomise E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer Ann. Thorac. Surg., March 1, 2001; 71(3): 949 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. van de Wetering, N. Barker, I. C. Harkes, M. van der Heyden, N. J. Dijk, A. Hollestelle, J. G. M. Klijn, H. Clevers, and M. Schutte Mutant E-cadherin Breast Cancer Cells Do Not Display Constitutive Wnt Signaling Cancer Res., January 1, 2001; 61(1): 278 - 284. [Abstract] [Full Text]
|
|
|
|
|
|
K. El Abdaimi, N. Dion, V. Papavasiliou, P.-E. Cardinal, L. Binderup, D. Goltzman, L.-G. Ste-Marie, and R. Kremer The Vitamin D Analogue EB 1089 Prevents Skeletal Metastasis and Prolongs Survival Time in Nude Mice Transplanted with Human Breast Cancer Cells Cancer Res., August 1, 2000; 60(16): 4412 - 4418. [Abstract] [Full Text]
|
|
|
|
 |
|
 M.-Y. Hsu, F. E. Meier, M. Nesbit, J.-Y. Hsu, P. Van Belle, D. E. Elder, and M. Herlyn E-Cadherin Expression in Melanoma Cells Restores Keratinocyte-Mediated Growth Control and Down-Regulates Expression of Invasion-Related Adhesion Receptors Am. J. Pathol., May 1, 2000; 156(5): 1515 - 1525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M von Schlippe, J. Marshall, P Perry, M Stone, A. Zhu, and I. Hart Functional interaction between E-cadherin and alphav-containing integrins in carcinoma cells J. Cell Sci., January 2, 2000; 113(3): 425 - 437. [Abstract] [PDF]
|
|
|
|
|
|
B. Nawrocki, M. Polette, J. Van Hengel, J.-M. Tournier, F. Van Roy, and P. Birembaut Cytoplasmic Redistribution of E-Cadherin-Catenin Adhesion Complex Is Associated with Down-Regulated Tyrosine Phosphorylation of E-Cadherin in Human Bronchopulmonary Carcinomas Am. J. Pathol., November 1, 1998; 153(5): 1521 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Guise and G. R. Mundy Cancer and Bone Endocr. Rev., February 1, 1998; 19(1): 18 - 54. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Gniadecki, B. Gajkowska, and M. Hansen 1,25-Dihydroxyvitamin D3 Stimulates the Assembly of Adherens Junctions in Keratinocytes: Involvement of Protein Kinase C Endocrinology, June 1, 1997; 138(6): 2241 - 2248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Poser, D. Dominguez, A. G. de Herreros, A. Varnai, R. Buettner, and A. K Bosserhoff Loss of E-cadherin Expression in Melanoma Cells Involves Up-regulation of the Transcriptional Repressor Snail J. Biol. Chem., June 29, 2001; 276(27): 24661 - 24666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abdel-Ghany, H.-C. Cheng, R. C. Elble, and B. U. Pauli The Breast Cancer beta 4 Integrin and Endothelial Human CLCA2 Mediate Lung Metastasis J. Biol. Chem., June 29, 2001; 276(27): 25438 - 25446. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
