Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity
Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with r...
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| Veröffentlicht in: | Experimental cell research 2005-07, Vol.307 (1), p.194-203 |
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| creator | Nishida, Yoshihiro Knudson, Warren Knudson, Cheryl B. Ishiguro, Naoki |
| description | Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion. |
| doi_str_mv | 10.1016/j.yexcr.2005.03.026 |
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The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1016/j.yexcr.2005.03.026</identifier><identifier>PMID: 15922739</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; BIOLOGICAL ACCUMULATION ; Bone Neoplasms - chemistry ; Bone Neoplasms - genetics ; Bone Neoplasms - pathology ; Cell Line, Tumor ; Cell Movement - drug effects ; CELL PROLIFERATION ; Cell Proliferation - drug effects ; Chemotaxis - drug effects ; Collagen - drug effects ; Drug Combinations ; Gene Dosage ; Glucuronosyltransferase - antagonists & inhibitors ; Glucuronosyltransferase - genetics ; Humans ; Hyaluronan ; Hyaluronan synthase ; Hyaluronan Synthases ; Hyaluronic Acid - biosynthesis ; Hyaluronic Acid - metabolism ; INHIBITION ; Kinetics ; Laminin - drug effects ; MG-63 ; OLIGONUCLEOTIDES ; Oligonucleotides, Antisense - pharmacology ; Osteosarcoma ; Osteosarcoma - chemistry ; Osteosarcoma - genetics ; Osteosarcoma - pathology ; OSTEOSARCOMAS ; POLYMERASE CHAIN REACTION ; Proteoglycans - drug effects ; RETENTION ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - antagonists & inhibitors ; SKELETON</subject><ispartof>Experimental cell research, 2005-07, Vol.307 (1), p.194-203</ispartof><rights>2005 Elsevier Inc.</rights><rights>Copyright © 2005 Elsevier B.V. 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The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>BIOLOGICAL ACCUMULATION</subject><subject>Bone Neoplasms - chemistry</subject><subject>Bone Neoplasms - genetics</subject><subject>Bone Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>CELL PROLIFERATION</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemotaxis - drug effects</subject><subject>Collagen - drug effects</subject><subject>Drug Combinations</subject><subject>Gene Dosage</subject><subject>Glucuronosyltransferase - antagonists & inhibitors</subject><subject>Glucuronosyltransferase - genetics</subject><subject>Humans</subject><subject>Hyaluronan</subject><subject>Hyaluronan synthase</subject><subject>Hyaluronan Synthases</subject><subject>Hyaluronic Acid - biosynthesis</subject><subject>Hyaluronic Acid - metabolism</subject><subject>INHIBITION</subject><subject>Kinetics</subject><subject>Laminin - drug effects</subject><subject>MG-63</subject><subject>OLIGONUCLEOTIDES</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma - chemistry</subject><subject>Osteosarcoma - genetics</subject><subject>Osteosarcoma - pathology</subject><subject>OSTEOSARCOMAS</subject><subject>POLYMERASE CHAIN REACTION</subject><subject>Proteoglycans - drug effects</subject><subject>RETENTION</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - antagonists & inhibitors</subject><subject>SKELETON</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAUhSMEokPhFyChCCR2Ga6vHSdegFRV5SFVYgNry-PcaTya2MVOKsKvr9MZoLCAlSX7O-c-fIriOYM1Aybf7NYzfbdxjQD1GvgaUD4oVgwUVCgQHxYrACYq0WJzUjxJaQcAbcvk4-KE1Qqx4WpV_Djzo0vkE5XO927jRhd8GbZlP5v9FIM3vkyzH3uTqMLMlP005LuQRgrJRBsGU1ra79NPfbovjTSSv7M0vivHaQjRXZF31o3z0-LR1uwTPTuep8XX9xdfzj9Wl58_fDo_u6ysBDVWQiizMdiR2JLkdbcRjCPvCLG2nLfA65oxqywjSchrxdoaFIIRsmUM1ZafFu8OvtfTZqDO5oai2evr6AYTZx2M03--eNfrq3CjOWtRKMgGrw4GeWinU-6dbG-D92RHjdCwRiJm6vWxTAzfJkqjHlxaNmM8hSlp2bRNA1z-F0TIbkosdV_-Be7CFH3elWZKyKZh0GaIHyAbQ0qRtr8GY6CXnOidvsuJXnKigeuck6x6cX8nvzXHYGTg7QGg_DM3juIyN3lLnYvL2F1w_yxwC33l0cw</recordid><startdate>20050701</startdate><enddate>20050701</enddate><creator>Nishida, Yoshihiro</creator><creator>Knudson, Warren</creator><creator>Knudson, Cheryl B.</creator><creator>Ishiguro, Naoki</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>7QP</scope><scope>7X8</scope><scope>OTOTI</scope><scope>5PM</scope></search><sort><creationdate>20050701</creationdate><title>Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity</title><author>Nishida, Yoshihiro ; Knudson, Warren ; Knudson, Cheryl B. ; Ishiguro, Naoki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c609t-449aba2de4fe635db41323de225c338035511c9c1e6e23591850920a4681129f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>BIOLOGICAL ACCUMULATION</topic><topic>Bone Neoplasms - chemistry</topic><topic>Bone Neoplasms - genetics</topic><topic>Bone Neoplasms - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>CELL PROLIFERATION</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemotaxis - drug effects</topic><topic>Collagen - drug effects</topic><topic>Drug Combinations</topic><topic>Gene Dosage</topic><topic>Glucuronosyltransferase - antagonists & inhibitors</topic><topic>Glucuronosyltransferase - genetics</topic><topic>Humans</topic><topic>Hyaluronan</topic><topic>Hyaluronan synthase</topic><topic>Hyaluronan Synthases</topic><topic>Hyaluronic Acid - biosynthesis</topic><topic>Hyaluronic Acid - metabolism</topic><topic>INHIBITION</topic><topic>Kinetics</topic><topic>Laminin - drug effects</topic><topic>MG-63</topic><topic>OLIGONUCLEOTIDES</topic><topic>Oligonucleotides, Antisense - pharmacology</topic><topic>Osteosarcoma</topic><topic>Osteosarcoma - chemistry</topic><topic>Osteosarcoma - genetics</topic><topic>Osteosarcoma - pathology</topic><topic>OSTEOSARCOMAS</topic><topic>POLYMERASE CHAIN REACTION</topic><topic>Proteoglycans - drug effects</topic><topic>RETENTION</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - antagonists & inhibitors</topic><topic>SKELETON</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishida, Yoshihiro</creatorcontrib><creatorcontrib>Knudson, Warren</creatorcontrib><creatorcontrib>Knudson, Cheryl B.</creatorcontrib><creatorcontrib>Ishiguro, Naoki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishida, Yoshihiro</au><au>Knudson, Warren</au><au>Knudson, Cheryl B.</au><au>Ishiguro, Naoki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity</atitle><jtitle>Experimental cell research</jtitle><addtitle>Exp Cell Res</addtitle><date>2005-07-01</date><risdate>2005</risdate><volume>307</volume><issue>1</issue><spage>194</spage><epage>203</epage><pages>194-203</pages><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15922739</pmid><doi>10.1016/j.yexcr.2005.03.026</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES BIOLOGICAL ACCUMULATION Bone Neoplasms - chemistry Bone Neoplasms - genetics Bone Neoplasms - pathology Cell Line, Tumor Cell Movement - drug effects CELL PROLIFERATION Cell Proliferation - drug effects Chemotaxis - drug effects Collagen - drug effects Drug Combinations Gene Dosage Glucuronosyltransferase - antagonists & inhibitors Glucuronosyltransferase - genetics Humans Hyaluronan Hyaluronan synthase Hyaluronan Synthases Hyaluronic Acid - biosynthesis Hyaluronic Acid - metabolism INHIBITION Kinetics Laminin - drug effects MG-63 OLIGONUCLEOTIDES Oligonucleotides, Antisense - pharmacology Osteosarcoma Osteosarcoma - chemistry Osteosarcoma - genetics Osteosarcoma - pathology OSTEOSARCOMAS POLYMERASE CHAIN REACTION Proteoglycans - drug effects RETENTION Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - antagonists & inhibitors SKELETON |
| title | Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity |
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