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§§§
From the Departments of Oncology,*
Pathology,§
and
Surgery,¶
Kuopio University Hospital; and
the Departments of Anatomy
and Pathology and Forensic
Medicine,
University of Kuopio,
Kuopio, Finland
Hyaluronan (HA) is an extracellular matrix polysaccharide that promotes cell migration through its cell surface receptors and by effecting changes in the physical environment. HA expression is frequently increased in malignant tumors, whereas its association with the invasive potential and patient outcome in breast cancer has not been reported. The localization and signal intensity of HA was analyzed in 143 paraffin-embedded tumor samples of human breast carcinoma using a biotinylated HA-specific probe. In the immediate peritumoral stroma, HA signal was moderately or strongly increased in 39% and 56% of the cases, respectively. Normal ductal epithelium showed no HA, whereas in 57% of the tumors at least some of the carcinoma cells were HA positive. The intensity of the stromal HA signal and the presence of cell-associated HA were both significantly related to poor differentiation of the tumors, axillary lymph node positivity, and short overall survival of the patients. In Cox’s multivariate analysis, both the intensity of stromal HA signal alone and that combined with the HA positivity in tumor cells were independent prognostic factors for overall survival. These results suggest that HA is directly involved in the spreading of breast cancer and may offer a potential target for new therapies.
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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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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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J.-P. Pienimaki, K. Rilla, C. Fulop, R. K. Sironen, S. Karvinen, S. Pasonen, M. J. Lammi, R. Tammi, V. C. Hascall, and M. I. Tammi Epidermal Growth Factor Activates Hyaluronan Synthase 2 in Epidermal Keratinocytes and Increases Pericellular and Intracellular Hyaluronan J. Biol. Chem., June 1, 2001; 276(23): 20428 - 20435. [Abstract] [Full Text] [PDF]
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V. B. Lokeshwar, D. Rubinowicz, G. L. Schroeder, E. Forgacs, J. D. Minna, N. L. Block, M. Nadji, and B. L. Lokeshwar Stromal and Epithelial Expression of Tumor Markers Hyaluronic Acid and HYAL1 Hyaluronidase in Prostate Cancer J. Biol. Chem., April 6, 2001; 276(15): 11922 - 11932. [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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