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Tumor Biology |
The Burnham Institute, La Jolla, California 92037
Hyaluronan (HA) has long been implicated in malignant transformation and tumor progression. However, due to the lack of molecular tools to directly manipulate production of HA, which does not require a core protein for its synthesis, our understanding of the role of HA in tumor cells has been largely circumstantial. In this study, we genetically manipulated the production of HA by transfection of a mammalian HA synthase Has2 into human HT1080 cells and examined the malignant phenotype of transfected cells. We found that increased production of HA promotes anchorage-independent growth and tumorigenicity of the cells. Has2-transfected cells formed greater numbers of colonies in semisolid medium. Tumors in nude mice derived from Has2-transfected cells grew more rapidly and were 2–4 times larger than those derived from control cells at termination of experiments. Histological and biochemical analyses of tumors revealed no significant differences in cell density and tissue structures between them, indicating that the larger size of the tumors was due to enhanced cell proliferation, not to increased accumulation of tumor stroma or increased angiogenesis. These results demonstrate that HA production by tumor cells per se promotes proliferation of these cells in tissues and provides direct evidence for the role of HA in tumorigenicity.
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 N. Itano, F. Atsumi, T. Sawai, Y. Yamada, O. Miyaishi, T. Senga, M. Hamaguchi, and K. Kimata Abnormal accumulation of hyaluronan matrix diminishes contact inhibition of cell growth and promotes cell migration PNAS, March 19, 2002; 99(6): 3609 - 3614. [Abstract] [Full Text] [PDF]
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M. A. Simpson, C. M. Wilson, L. T. Furcht, A. P. Spicer, T. R. Oegema Jr., and J. B. McCarthy Manipulation of Hyaluronan Synthase Expression in Prostate Adenocarcinoma Cells Alters Pericellular Matrix Retention and Adhesion to Bone Marrow Endothelial Cells J. Biol. Chem., March 15, 2002; 277(12): 10050 - 10057. [Abstract] [Full Text] [PDF]
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B. P. Toole Hyaluronan promotes the malignant phenotype Glycobiology, March 1, 2002; 12(3): 37R - 42R. [Abstract] [Full Text] [PDF]
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M. I. Tammi, A. J. Day, and E. A. Turley Hyaluronan and Homeostasis: A Balancing Act J. Biol. Chem., February 8, 2002; 277(7): 4581 - 4584. [Full Text] [PDF]
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B. P. Toole, T. N. Wight, and M. I. Tammi Hyaluronan-Cell Interactions in Cancer and Vascular Disease J. Biol. Chem., February 8, 2002; 277(7): 4593 - 4596. [Full Text] [PDF]
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C. L. Nutt, C. A. Zerillo, G. M. Kelly, and S. Hockfield Brain Enriched Hyaluronan Binding (BEHAB)/Brevican Increases Aggressiveness of CNS-1 Gliomas in Lewis Rats Cancer Res., October 1, 2001; 61(19): 7056 - 7059. [Abstract] [Full Text] [PDF]
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N. Liu, F. Gao, Z. Han, X. Xu, C. B. Underhill, and L. Zhang Hyaluronan Synthase 3 Overexpression Promotes the Growth of TSU Prostate Cancer Cells Cancer Res., July 1, 2001; 61(13): 5207 - 5214. [Abstract] [Full Text] [PDF]
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 Y. Sohara, N. Ishiguro, K. Machida, H. Kurata, A. A. Thant, T. Senga, S. Matsuda, K. Kimata, H. Iwata, and M. Hamaguchi Hyaluronan Activates Cell Motility of v-Src-transformed Cells via Ras-Mitogen-activated Protein Kinase and Phosphoinositide 3-Kinase-Akt in a Tumor-specific Manner Mol. Biol. Cell, June 1, 2001; 12(6): 1859 - 1868. [Abstract] [Full Text] [PDF]
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J. M. Karjalainen, R. H. Tammi, M. I. Tammi, M. J. Eskelinen, U. M. Agren, J. J. Parkkinen, E. M. Alhava, and V.-M. Kosma Reduced Level of CD44 and Hyaluronan Associated with Unfavorable Prognosis in Clinical Stage I Cutaneous Melanoma Am. J. Pathol., September 1, 2000; 157(3): 957 - 965. [Abstract] [Full Text] [PDF]
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R. M. Peterson, Q. Yu, I. Stamenkovic, and B. P. Toole Perturbation of Hyaluronan Interactions by Soluble CD44 Inhibits Growth of Murine Mammary Carcinoma Cells in Ascites Am. J. Pathol., June 1, 2000; 156(6): 2159 - 2167. [Abstract] [Full Text] [PDF]
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M. A. Anttila, R. H. Tammi, M. I. Tammi, K. J. Syrjänen, S. V. Saarikoski, and V.-M. Kosma High Levels of Stromal Hyaluronan Predict Poor Disease Outcome in Epithelial Ovarian Cancer Cancer Res., January 1, 2000; 60(1): 150 - 155. [Abstract] [Full Text]
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L. Huang, N. Grammatikakis, M. Yoneda, S. D. Banerjee, and B. P. Toole Molecular Characterization of a Novel Intracellular Hyaluronan-binding Protein J. Biol. Chem., September 15, 2000; 275(38): 29829 - 29839. [Abstract] [Full Text] [PDF]
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M. A. Simpson, J. Reiland, S. R. Burger, L. T. Furcht, A. P. Spicer, T. R. Oegema Jr., and J. B. McCarthy Hyaluronan Synthase Elevation in Metastatic Prostate Carcinoma Cells Correlates with Hyaluronan Surface Retention, a Prerequisite for Rapid Adhesion to Bone Marrow Endothelial Cells J. Biol. Chem., May 18, 2001; 276(21): 17949 - 17957. [Abstract] [Full Text] [PDF]
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