Therapeutic potential of hyaluronan oligosaccharides for bone metastasis of breast cancer
Hyaluronan (HA) oligosaccharides were reported to have suppressive effects on various malignant tumors via disruption of receptor HA interactions. However, no studies have focused on the effects of HA oligosaccharides on bone metastasis of breast cancer. In this study, we clarified the effective siz...
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| Veröffentlicht in: | Journal of orthopaedic research 2012-04, Vol.30 (4), p.662-672 |
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| creator | Urakawa, Hiroshi Nishida, Yoshihiro Knudson, Warren Knudson, Cheryl B. Arai, Eisuke Kozawa, Eiji Futamura, Naohisa Wasa, Junji Ishiguro, Naoki |
| description | Hyaluronan (HA) oligosaccharides were reported to have suppressive effects on various malignant tumors via disruption of receptor HA interactions. However, no studies have focused on the effects of HA oligosaccharides on bone metastasis of breast cancer. In this study, we clarified the effective size of HA oligosaccharides required to inhibit cell growth in the highly invasive breast cancer cell line, MDA‐MB‐231 cells. Based on the results of cell growth assay, we subsequently analyzed the effects of HA tetrasaccharides, HA decasaccharides, and high molecular weight HA on the other breast cancer cell behaviors in vitro and breast cancer bone metastasis in vivo. HA decasaccharides significantly inhibited cell growth, motility, and invasion, whereas tetrasaccharides did not. HAS2 mRNA expression was altered after the treatment with both tetrasaccharides and decasaccharides. Phosphorylation of Akt was suppressed after 1 h treatment with HA decasaccharides, and the effect was partially reversed by anti‐CD44 monoclonal antibody. In vivo, local application of HA decasaccharides inhibited the expansion of osteolytic lesions in tibia on soft X‐rays using mouse bone metastasis model of breast cancer. Histological analysis revealed HA accumulation in bone metastatic lesions was perturbed by decasaccharides. These results suggest that HA oligosaccharides suppressed progression of bone metastasis in breast cancer via interruption of endogenous HA–CD44 interaction, and as such, can be a novel therapeutic candidate to limit bone metastasis of breast cancer. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:662–672, 2012 |
| doi_str_mv | 10.1002/jor.21557 |
| format | Article |
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However, no studies have focused on the effects of HA oligosaccharides on bone metastasis of breast cancer. In this study, we clarified the effective size of HA oligosaccharides required to inhibit cell growth in the highly invasive breast cancer cell line, MDA‐MB‐231 cells. Based on the results of cell growth assay, we subsequently analyzed the effects of HA tetrasaccharides, HA decasaccharides, and high molecular weight HA on the other breast cancer cell behaviors in vitro and breast cancer bone metastasis in vivo. HA decasaccharides significantly inhibited cell growth, motility, and invasion, whereas tetrasaccharides did not. HAS2 mRNA expression was altered after the treatment with both tetrasaccharides and decasaccharides. Phosphorylation of Akt was suppressed after 1 h treatment with HA decasaccharides, and the effect was partially reversed by anti‐CD44 monoclonal antibody. In vivo, local application of HA decasaccharides inhibited the expansion of osteolytic lesions in tibia on soft X‐rays using mouse bone metastasis model of breast cancer. Histological analysis revealed HA accumulation in bone metastatic lesions was perturbed by decasaccharides. These results suggest that HA oligosaccharides suppressed progression of bone metastasis in breast cancer via interruption of endogenous HA–CD44 interaction, and as such, can be a novel therapeutic candidate to limit bone metastasis of breast cancer. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:662–672, 2012</description><identifier>ISSN: 0736-0266</identifier><identifier>EISSN: 1554-527X</identifier><identifier>DOI: 10.1002/jor.21557</identifier><identifier>PMID: 21913222</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; bone ; Bone Neoplasms - drug therapy ; Bone Neoplasms - secondary ; breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cell Division - drug effects ; Cell Line, Tumor ; Cell Movement - drug effects ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Glucuronosyltransferase - genetics ; Humans ; hyaluronan ; hyaluronan oligosaccharides ; Hyaluronan Receptors - genetics ; Hyaluronan Synthases ; Hyaluronic Acid - pharmacology ; metastasis ; Mice ; Neoplasm Invasiveness - pathology ; NIH 3T3 Cells ; Oligosaccharides - pharmacology ; Phosphorylation - drug effects ; Proto-Oncogene Proteins c-akt - metabolism ; Tibia - pathology ; Viscosupplements - pharmacology ; Xenograft Model Antitumor Assays</subject><ispartof>Journal of orthopaedic research, 2012-04, Vol.30 (4), p.662-672</ispartof><rights>Copyright © 2011 Orthopaedic Research Society</rights><rights>Copyright © 2011 Orthopaedic Research Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4637-6668e00cddc7aee0ff1df556c65d25116bfb6d794c584649fe4e64f982718afa3</citedby><cites>FETCH-LOGICAL-c4637-6668e00cddc7aee0ff1df556c65d25116bfb6d794c584649fe4e64f982718afa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjor.21557$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjor.21557$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21913222$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Urakawa, Hiroshi</creatorcontrib><creatorcontrib>Nishida, Yoshihiro</creatorcontrib><creatorcontrib>Knudson, Warren</creatorcontrib><creatorcontrib>Knudson, Cheryl B.</creatorcontrib><creatorcontrib>Arai, Eisuke</creatorcontrib><creatorcontrib>Kozawa, Eiji</creatorcontrib><creatorcontrib>Futamura, Naohisa</creatorcontrib><creatorcontrib>Wasa, Junji</creatorcontrib><creatorcontrib>Ishiguro, Naoki</creatorcontrib><title>Therapeutic potential of hyaluronan oligosaccharides for bone metastasis of breast cancer</title><title>Journal of orthopaedic research</title><addtitle>J. Orthop. Res</addtitle><description>Hyaluronan (HA) oligosaccharides were reported to have suppressive effects on various malignant tumors via disruption of receptor HA interactions. However, no studies have focused on the effects of HA oligosaccharides on bone metastasis of breast cancer. In this study, we clarified the effective size of HA oligosaccharides required to inhibit cell growth in the highly invasive breast cancer cell line, MDA‐MB‐231 cells. Based on the results of cell growth assay, we subsequently analyzed the effects of HA tetrasaccharides, HA decasaccharides, and high molecular weight HA on the other breast cancer cell behaviors in vitro and breast cancer bone metastasis in vivo. HA decasaccharides significantly inhibited cell growth, motility, and invasion, whereas tetrasaccharides did not. HAS2 mRNA expression was altered after the treatment with both tetrasaccharides and decasaccharides. Phosphorylation of Akt was suppressed after 1 h treatment with HA decasaccharides, and the effect was partially reversed by anti‐CD44 monoclonal antibody. In vivo, local application of HA decasaccharides inhibited the expansion of osteolytic lesions in tibia on soft X‐rays using mouse bone metastasis model of breast cancer. Histological analysis revealed HA accumulation in bone metastatic lesions was perturbed by decasaccharides. These results suggest that HA oligosaccharides suppressed progression of bone metastasis in breast cancer via interruption of endogenous HA–CD44 interaction, and as such, can be a novel therapeutic candidate to limit bone metastasis of breast cancer. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:662–672, 2012</description><subject>Animals</subject><subject>bone</subject><subject>Bone Neoplasms - drug therapy</subject><subject>Bone Neoplasms - secondary</subject><subject>breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Division - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Glucuronosyltransferase - genetics</subject><subject>Humans</subject><subject>hyaluronan</subject><subject>hyaluronan oligosaccharides</subject><subject>Hyaluronan Receptors - genetics</subject><subject>Hyaluronan Synthases</subject><subject>Hyaluronic Acid - pharmacology</subject><subject>metastasis</subject><subject>Mice</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>NIH 3T3 Cells</subject><subject>Oligosaccharides - pharmacology</subject><subject>Phosphorylation - drug effects</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Tibia - pathology</subject><subject>Viscosupplements - pharmacology</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0736-0266</issn><issn>1554-527X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kF1LwzAUhoMobn5c-Aekt150S9ImaS9l6HQMB2N-XYU0PXGdXVOSDt2_t7Nud8KBlwPP-148CF0RPCAY0-HKugEljIkj1G8jDhkVb8eoj0XEQ0w576Ez71cYY0Focop6lKQkopT20ftiCU7VsGkKHdS2gaopVBlYEyy3qtw4W6kqsGXxYb3SeqlckYMPjHVBZisI1tAo317hd5XMQfsFWlUa3AU6Mar0cPmX5-j5_m4xegins_Hj6HYa6phHIuScJ4CxznMtFAA2huSGMa45yykjhGcm47lIY82SmMepgRh4bNKECpIoo6JzdNPtame9d2Bk7Yq1cltJsNzpka0e-aunZa87tt5ka8gP5N5HCww74KsoYfv_kpzM5vvJsGsUvoHvQ0O5T8lFJJh8fRrLyeRlEY3GsZxHP2P0gDg</recordid><startdate>201204</startdate><enddate>201204</enddate><creator>Urakawa, Hiroshi</creator><creator>Nishida, Yoshihiro</creator><creator>Knudson, Warren</creator><creator>Knudson, Cheryl B.</creator><creator>Arai, Eisuke</creator><creator>Kozawa, Eiji</creator><creator>Futamura, Naohisa</creator><creator>Wasa, Junji</creator><creator>Ishiguro, Naoki</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201204</creationdate><title>Therapeutic potential of hyaluronan oligosaccharides for bone metastasis of breast cancer</title><author>Urakawa, Hiroshi ; Nishida, Yoshihiro ; Knudson, Warren ; Knudson, Cheryl B. ; Arai, Eisuke ; Kozawa, Eiji ; Futamura, Naohisa ; Wasa, Junji ; Ishiguro, Naoki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4637-6668e00cddc7aee0ff1df556c65d25116bfb6d794c584649fe4e64f982718afa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>bone</topic><topic>Bone Neoplasms - drug therapy</topic><topic>Bone Neoplasms - secondary</topic><topic>breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Division - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Glucuronosyltransferase - genetics</topic><topic>Humans</topic><topic>hyaluronan</topic><topic>hyaluronan oligosaccharides</topic><topic>Hyaluronan Receptors - genetics</topic><topic>Hyaluronan Synthases</topic><topic>Hyaluronic Acid - pharmacology</topic><topic>metastasis</topic><topic>Mice</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>NIH 3T3 Cells</topic><topic>Oligosaccharides - pharmacology</topic><topic>Phosphorylation - drug effects</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Tibia - pathology</topic><topic>Viscosupplements - pharmacology</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Urakawa, Hiroshi</creatorcontrib><creatorcontrib>Nishida, Yoshihiro</creatorcontrib><creatorcontrib>Knudson, Warren</creatorcontrib><creatorcontrib>Knudson, Cheryl B.</creatorcontrib><creatorcontrib>Arai, Eisuke</creatorcontrib><creatorcontrib>Kozawa, Eiji</creatorcontrib><creatorcontrib>Futamura, Naohisa</creatorcontrib><creatorcontrib>Wasa, Junji</creatorcontrib><creatorcontrib>Ishiguro, Naoki</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of orthopaedic research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Urakawa, Hiroshi</au><au>Nishida, Yoshihiro</au><au>Knudson, Warren</au><au>Knudson, Cheryl B.</au><au>Arai, Eisuke</au><au>Kozawa, Eiji</au><au>Futamura, Naohisa</au><au>Wasa, Junji</au><au>Ishiguro, Naoki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic potential of hyaluronan oligosaccharides for bone metastasis of breast cancer</atitle><jtitle>Journal of orthopaedic research</jtitle><addtitle>J. Orthop. Res</addtitle><date>2012-04</date><risdate>2012</risdate><volume>30</volume><issue>4</issue><spage>662</spage><epage>672</epage><pages>662-672</pages><issn>0736-0266</issn><eissn>1554-527X</eissn><abstract>Hyaluronan (HA) oligosaccharides were reported to have suppressive effects on various malignant tumors via disruption of receptor HA interactions. However, no studies have focused on the effects of HA oligosaccharides on bone metastasis of breast cancer. In this study, we clarified the effective size of HA oligosaccharides required to inhibit cell growth in the highly invasive breast cancer cell line, MDA‐MB‐231 cells. Based on the results of cell growth assay, we subsequently analyzed the effects of HA tetrasaccharides, HA decasaccharides, and high molecular weight HA on the other breast cancer cell behaviors in vitro and breast cancer bone metastasis in vivo. HA decasaccharides significantly inhibited cell growth, motility, and invasion, whereas tetrasaccharides did not. HAS2 mRNA expression was altered after the treatment with both tetrasaccharides and decasaccharides. Phosphorylation of Akt was suppressed after 1 h treatment with HA decasaccharides, and the effect was partially reversed by anti‐CD44 monoclonal antibody. In vivo, local application of HA decasaccharides inhibited the expansion of osteolytic lesions in tibia on soft X‐rays using mouse bone metastasis model of breast cancer. Histological analysis revealed HA accumulation in bone metastatic lesions was perturbed by decasaccharides. These results suggest that HA oligosaccharides suppressed progression of bone metastasis in breast cancer via interruption of endogenous HA–CD44 interaction, and as such, can be a novel therapeutic candidate to limit bone metastasis of breast cancer. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. 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| subjects | Animals bone Bone Neoplasms - drug therapy Bone Neoplasms - secondary breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cell Division - drug effects Cell Line, Tumor Cell Movement - drug effects Disease Models, Animal Female Gene Expression Regulation, Neoplastic - drug effects Glucuronosyltransferase - genetics Humans hyaluronan hyaluronan oligosaccharides Hyaluronan Receptors - genetics Hyaluronan Synthases Hyaluronic Acid - pharmacology metastasis Mice Neoplasm Invasiveness - pathology NIH 3T3 Cells Oligosaccharides - pharmacology Phosphorylation - drug effects Proto-Oncogene Proteins c-akt - metabolism Tibia - pathology Viscosupplements - pharmacology Xenograft Model Antitumor Assays |
| title | Therapeutic potential of hyaluronan oligosaccharides for bone metastasis of breast cancer |
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