Hyaluronan in human malignancies |
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Authors: | Sironen R K Tammi M Tammi R Auvinen P K Anttila M Kosma V-M |
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Institution: | aInstitute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland;bInstitute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland;cDepartment of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland;dDepartment of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland;eDepartment of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland |
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Abstract: | Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma–cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial–mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance. |
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Keywords: | Abbreviations: ECM extracellular matrix HA hyaluronan HAS hyaluronan synthase RHAMM receptor for hyaluronan-mediated motility EMT epithelial&ndash mesenchymal transition ROS reactive oxygen species SCC squamous cell carcinoma EMMPRIN extracellular matrix metalloproteinase inducer MMP matrix metalloproteinase HGF hepatocyte growth factor SDF-1 stromal cell-derived factor-1 TIAM-1 T-cell lymphoma invasion and metastasis 1 TLR-4 Toll-like receptor-4 |
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