Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor–positive breast carcinoma models
We investigated the significance of erythropoietin receptor (EPOR) expression following treatment with recombinant human erythropoietin (rHuEPO; epoetin α) and the effect of recombinant epoetins (epoetin α, epoetin β, and darbepoetin α) alone or in combination with anticancer therapy on tumor growth...
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| Veröffentlicht in: | Molecular cancer therapeutics 2006-02, Vol.5 (2), p.347-355 |
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| creator | LaMontagne, Kenneth R Butler, Jeannene Marshall, Deborah J Tullai, Jennifer Gechtman, Ze'ev Hall, Chassidy Meshaw, Alan Farrell, Francis X |
| description | We investigated the significance of erythropoietin receptor (EPOR) expression following treatment with recombinant human erythropoietin
(rHuEPO; epoetin α) and the effect of recombinant epoetins (epoetin α, epoetin β, and darbepoetin α) alone or in combination
with anticancer therapy on tumor growth in two well-established preclinical models of breast carcinoma (MDA-MB-231 and MCF-7
cell lines). Expression and localization of EPOR under hypoxic and normoxic conditions in MDA-MB-231 and MCF-7 cells were
evaluated by immunoblotting, flow cytometry, and immunohistochemistry. EPOR binding was evaluated using [ 125 I]rHuEPO. Proliferation, migration, and signaling in MDA-MB-231 and MCF-7 cells following treatment with rHuEPO were evaluated.
Tumor growth was assessed following administration of recombinant epoetins alone and in combination with paclitaxel (anticancer
therapy) in orthotopically implanted MDA-MB-231 and MCF-7 breast carcinoma xenograft models in athymic mice. EPOR expression
was detected in both tumor cell lines. EPOR localization was found to be exclusively cytosolic and no specific [ 125 I]rHuEPO binding was observed. There was no stimulated migration, proliferation, or activation of mitogen-activated protein
kinase and AKT following rHuEPO treatment. In mice, treatment with recombinant epoetins alone and in combination with paclitaxel
resulted in equivalent tumor burdens compared with vehicle-treated controls. Results from our study suggest that although
EPOR expression was observed in two well-established breast carcinoma cell lines, it was localized to a cytosolic distribution
and did not transduce a signaling cascade in tumors that leads to tumor growth. The addition of recombinant epoetins to paclitaxel
did not affect the outcome of paclitaxel therapy in breast carcinoma xenograft models. These results show that recombinant
epoetins do not evoke a physiologic response on EPOR-bearing tumor cells as assessed by numerous variables, including growth,
migration, and cytotoxic challenge in preclinical in vivo tumor models. [Mol Cancer Ther 2006;5(2):347–55] |
| doi_str_mv | 10.1158/1535-7163.MCT-05-0203 |
| format | Article |
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(rHuEPO; epoetin α) and the effect of recombinant epoetins (epoetin α, epoetin β, and darbepoetin α) alone or in combination
with anticancer therapy on tumor growth in two well-established preclinical models of breast carcinoma (MDA-MB-231 and MCF-7
cell lines). Expression and localization of EPOR under hypoxic and normoxic conditions in MDA-MB-231 and MCF-7 cells were
evaluated by immunoblotting, flow cytometry, and immunohistochemistry. EPOR binding was evaluated using [ 125 I]rHuEPO. Proliferation, migration, and signaling in MDA-MB-231 and MCF-7 cells following treatment with rHuEPO were evaluated.
Tumor growth was assessed following administration of recombinant epoetins alone and in combination with paclitaxel (anticancer
therapy) in orthotopically implanted MDA-MB-231 and MCF-7 breast carcinoma xenograft models in athymic mice. EPOR expression
was detected in both tumor cell lines. EPOR localization was found to be exclusively cytosolic and no specific [ 125 I]rHuEPO binding was observed. There was no stimulated migration, proliferation, or activation of mitogen-activated protein
kinase and AKT following rHuEPO treatment. In mice, treatment with recombinant epoetins alone and in combination with paclitaxel
resulted in equivalent tumor burdens compared with vehicle-treated controls. Results from our study suggest that although
EPOR expression was observed in two well-established breast carcinoma cell lines, it was localized to a cytosolic distribution
and did not transduce a signaling cascade in tumors that leads to tumor growth. The addition of recombinant epoetins to paclitaxel
did not affect the outcome of paclitaxel therapy in breast carcinoma xenograft models. These results show that recombinant
epoetins do not evoke a physiologic response on EPOR-bearing tumor cells as assessed by numerous variables, including growth,
migration, and cytotoxic challenge in preclinical in vivo tumor models. [Mol Cancer Ther 2006;5(2):347–55]</description><identifier>ISSN: 1535-7163</identifier><identifier>EISSN: 1538-8514</identifier><identifier>DOI: 10.1158/1535-7163.MCT-05-0203</identifier><identifier>PMID: 16505108</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Animals ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; breast carcinoma ; Breast Neoplasms - chemistry ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Carcinoma - chemistry ; Carcinoma - drug therapy ; Carcinoma - metabolism ; Cell Hypoxia ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; epoetin α ; Erythropoietin - adverse effects ; Erythropoietin - therapeutic use ; erythropoietin receptor ; Female ; Humans ; Mice ; Mice, Nude ; Mitogen-Activated Protein Kinase Kinases - metabolism ; Paclitaxel - therapeutic use ; Proto-Oncogene Proteins c-akt - metabolism ; Receptors, Erythropoietin - analysis ; Receptors, Erythropoietin - metabolism ; recombinant epoetins ; Recombinant Proteins ; tumor growth ; Xenograft Model Antitumor Assays</subject><ispartof>Molecular cancer therapeutics, 2006-02, Vol.5 (2), p.347-355</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-499fc14e3d4388c7294ce3f00469cbcfe5756182c33bda5f379983141aff6353</citedby><cites>FETCH-LOGICAL-c416t-499fc14e3d4388c7294ce3f00469cbcfe5756182c33bda5f379983141aff6353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3342,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16505108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LaMontagne, Kenneth R</creatorcontrib><creatorcontrib>Butler, Jeannene</creatorcontrib><creatorcontrib>Marshall, Deborah J</creatorcontrib><creatorcontrib>Tullai, Jennifer</creatorcontrib><creatorcontrib>Gechtman, Ze'ev</creatorcontrib><creatorcontrib>Hall, Chassidy</creatorcontrib><creatorcontrib>Meshaw, Alan</creatorcontrib><creatorcontrib>Farrell, Francis X</creatorcontrib><title>Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor–positive breast carcinoma models</title><title>Molecular cancer therapeutics</title><addtitle>Mol Cancer Ther</addtitle><description>We investigated the significance of erythropoietin receptor (EPOR) expression following treatment with recombinant human erythropoietin
(rHuEPO; epoetin α) and the effect of recombinant epoetins (epoetin α, epoetin β, and darbepoetin α) alone or in combination
with anticancer therapy on tumor growth in two well-established preclinical models of breast carcinoma (MDA-MB-231 and MCF-7
cell lines). Expression and localization of EPOR under hypoxic and normoxic conditions in MDA-MB-231 and MCF-7 cells were
evaluated by immunoblotting, flow cytometry, and immunohistochemistry. EPOR binding was evaluated using [ 125 I]rHuEPO. Proliferation, migration, and signaling in MDA-MB-231 and MCF-7 cells following treatment with rHuEPO were evaluated.
Tumor growth was assessed following administration of recombinant epoetins alone and in combination with paclitaxel (anticancer
therapy) in orthotopically implanted MDA-MB-231 and MCF-7 breast carcinoma xenograft models in athymic mice. EPOR expression
was detected in both tumor cell lines. EPOR localization was found to be exclusively cytosolic and no specific [ 125 I]rHuEPO binding was observed. There was no stimulated migration, proliferation, or activation of mitogen-activated protein
kinase and AKT following rHuEPO treatment. In mice, treatment with recombinant epoetins alone and in combination with paclitaxel
resulted in equivalent tumor burdens compared with vehicle-treated controls. Results from our study suggest that although
EPOR expression was observed in two well-established breast carcinoma cell lines, it was localized to a cytosolic distribution
and did not transduce a signaling cascade in tumors that leads to tumor growth. The addition of recombinant epoetins to paclitaxel
did not affect the outcome of paclitaxel therapy in breast carcinoma xenograft models. These results show that recombinant
epoetins do not evoke a physiologic response on EPOR-bearing tumor cells as assessed by numerous variables, including growth,
migration, and cytotoxic challenge in preclinical in vivo tumor models. [Mol Cancer Ther 2006;5(2):347–55]</description><subject>Animals</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>breast carcinoma</subject><subject>Breast Neoplasms - chemistry</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Carcinoma - chemistry</subject><subject>Carcinoma - drug therapy</subject><subject>Carcinoma - metabolism</subject><subject>Cell Hypoxia</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>epoetin α</subject><subject>Erythropoietin - adverse effects</subject><subject>Erythropoietin - therapeutic use</subject><subject>erythropoietin receptor</subject><subject>Female</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mitogen-Activated Protein Kinase Kinases - metabolism</subject><subject>Paclitaxel - therapeutic use</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors, Erythropoietin - analysis</subject><subject>Receptors, Erythropoietin - metabolism</subject><subject>recombinant epoetins</subject><subject>Recombinant Proteins</subject><subject>tumor growth</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1535-7163</issn><issn>1538-8514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1TAQhS0EoqXwCCCv2KV44p_YS3RFAakICd295TiTxiiJg-1Qdcc78IY8CQn3Sl2ymtHoOzOjcwh5DewaQOp3ILmsGlD8-svhWDFZsZrxJ-Rym-tKSxBP__Un5oK8yPk7Y6BNDc_JBSjJJDB9SZZv6OPUhtnNheISsYQ50y7SORaaS5jW0RWkZZ1ioncp3peBhplieihDiksMu4Am9LiUmP78-r3EHEr4ibRN6HKh3iUf5jg5OsUOx_ySPOvdmPHVuV6R482H4-FTdfv14-fD-9vKC1ClEsb0HgTyTnCtfVMb4ZH3jAllfOt7lI1UoGvPeds52fPGGM1BgOt7xSW_Im9Pa5cUf6yYi51C9jiObsa4ZqsaZZTaJP8DwYjaNJxtoDyBPsWcE_Z2SWFy6cECs3skdrfb7nbbLRLLpN0j2XRvzgfWdsLuUXXO4PGDIdwN9yGh9W72mBJm3MwbrLS15aLhfwHxBpiO</recordid><startdate>20060201</startdate><enddate>20060201</enddate><creator>LaMontagne, Kenneth R</creator><creator>Butler, Jeannene</creator><creator>Marshall, Deborah J</creator><creator>Tullai, Jennifer</creator><creator>Gechtman, Ze'ev</creator><creator>Hall, Chassidy</creator><creator>Meshaw, Alan</creator><creator>Farrell, Francis X</creator><general>American Association for Cancer Research</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20060201</creationdate><title>Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor–positive breast carcinoma models</title><author>LaMontagne, Kenneth R ; Butler, Jeannene ; Marshall, Deborah J ; Tullai, Jennifer ; Gechtman, Ze'ev ; Hall, Chassidy ; Meshaw, Alan ; Farrell, Francis X</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-499fc14e3d4388c7294ce3f00469cbcfe5756182c33bda5f379983141aff6353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>breast carcinoma</topic><topic>Breast Neoplasms - chemistry</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Carcinoma - chemistry</topic><topic>Carcinoma - drug therapy</topic><topic>Carcinoma - metabolism</topic><topic>Cell Hypoxia</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>epoetin α</topic><topic>Erythropoietin - adverse effects</topic><topic>Erythropoietin - therapeutic use</topic><topic>erythropoietin receptor</topic><topic>Female</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mitogen-Activated Protein Kinase Kinases - metabolism</topic><topic>Paclitaxel - therapeutic use</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptors, Erythropoietin - analysis</topic><topic>Receptors, Erythropoietin - metabolism</topic><topic>recombinant epoetins</topic><topic>Recombinant Proteins</topic><topic>tumor growth</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LaMontagne, Kenneth R</creatorcontrib><creatorcontrib>Butler, Jeannene</creatorcontrib><creatorcontrib>Marshall, Deborah J</creatorcontrib><creatorcontrib>Tullai, Jennifer</creatorcontrib><creatorcontrib>Gechtman, Ze'ev</creatorcontrib><creatorcontrib>Hall, Chassidy</creatorcontrib><creatorcontrib>Meshaw, Alan</creatorcontrib><creatorcontrib>Farrell, Francis X</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LaMontagne, Kenneth R</au><au>Butler, Jeannene</au><au>Marshall, Deborah J</au><au>Tullai, Jennifer</au><au>Gechtman, Ze'ev</au><au>Hall, Chassidy</au><au>Meshaw, Alan</au><au>Farrell, Francis X</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor–positive breast carcinoma models</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2006-02-01</date><risdate>2006</risdate><volume>5</volume><issue>2</issue><spage>347</spage><epage>355</epage><pages>347-355</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>We investigated the significance of erythropoietin receptor (EPOR) expression following treatment with recombinant human erythropoietin
(rHuEPO; epoetin α) and the effect of recombinant epoetins (epoetin α, epoetin β, and darbepoetin α) alone or in combination
with anticancer therapy on tumor growth in two well-established preclinical models of breast carcinoma (MDA-MB-231 and MCF-7
cell lines). Expression and localization of EPOR under hypoxic and normoxic conditions in MDA-MB-231 and MCF-7 cells were
evaluated by immunoblotting, flow cytometry, and immunohistochemistry. EPOR binding was evaluated using [ 125 I]rHuEPO. Proliferation, migration, and signaling in MDA-MB-231 and MCF-7 cells following treatment with rHuEPO were evaluated.
Tumor growth was assessed following administration of recombinant epoetins alone and in combination with paclitaxel (anticancer
therapy) in orthotopically implanted MDA-MB-231 and MCF-7 breast carcinoma xenograft models in athymic mice. EPOR expression
was detected in both tumor cell lines. EPOR localization was found to be exclusively cytosolic and no specific [ 125 I]rHuEPO binding was observed. There was no stimulated migration, proliferation, or activation of mitogen-activated protein
kinase and AKT following rHuEPO treatment. In mice, treatment with recombinant epoetins alone and in combination with paclitaxel
resulted in equivalent tumor burdens compared with vehicle-treated controls. Results from our study suggest that although
EPOR expression was observed in two well-established breast carcinoma cell lines, it was localized to a cytosolic distribution
and did not transduce a signaling cascade in tumors that leads to tumor growth. The addition of recombinant epoetins to paclitaxel
did not affect the outcome of paclitaxel therapy in breast carcinoma xenograft models. These results show that recombinant
epoetins do not evoke a physiologic response on EPOR-bearing tumor cells as assessed by numerous variables, including growth,
migration, and cytotoxic challenge in preclinical in vivo tumor models. [Mol Cancer Ther 2006;5(2):347–55]</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>16505108</pmid><doi>10.1158/1535-7163.MCT-05-0203</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular cancer therapeutics, 2006-02, Vol.5 (2), p.347-355 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | Animals Antineoplastic Combined Chemotherapy Protocols - therapeutic use breast carcinoma Breast Neoplasms - chemistry Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Carcinoma - chemistry Carcinoma - drug therapy Carcinoma - metabolism Cell Hypoxia Cell Movement - drug effects Cell Proliferation - drug effects epoetin α Erythropoietin - adverse effects Erythropoietin - therapeutic use erythropoietin receptor Female Humans Mice Mice, Nude Mitogen-Activated Protein Kinase Kinases - metabolism Paclitaxel - therapeutic use Proto-Oncogene Proteins c-akt - metabolism Receptors, Erythropoietin - analysis Receptors, Erythropoietin - metabolism recombinant epoetins Recombinant Proteins tumor growth Xenograft Model Antitumor Assays |
| title | Recombinant epoetins do not stimulate tumor growth in erythropoietin receptor–positive breast carcinoma models |
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