Phototheranostics of CD44-positive cell populations in triple negative breast cancer
Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies....
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| Veröffentlicht in: | Scientific reports 2016-06, Vol.6 (1), p.27871-27871, Article 27871 |
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| creator | Jin, Jiefu Krishnamachary, Balaji Mironchik, Yelena Kobayashi, Hisataka Bhujwalla, Zaver M. |
| description | Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44
high
/CD24
low
and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC. |
| doi_str_mv | 10.1038/srep27871 |
| format | Article |
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high
/CD24
low
and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep27871</identifier><identifier>PMID: 27302409</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 13/31 ; 13/51 ; 14/19 ; 64/60 ; 692/4017 ; 692/4028/67/1059/602 ; 692/4028/67/1347 ; 692/4028/67/71 ; Animals ; Antibodies, Monoclonal - chemistry ; Antibodies, Monoclonal - immunology ; Breast cancer ; Cell Death - drug effects ; Cell Line, Tumor ; Female ; Humanities and Social Sciences ; Humans ; Hyaluronan Receptors - immunology ; Hyaluronan Receptors - metabolism ; Immunoconjugates - chemistry ; Immunoconjugates - metabolism ; Immunoconjugates - pharmacology ; Immunotherapy - methods ; Irradiation ; Mice, Inbred BALB C ; Molecular Targeted Therapy - methods ; multidisciplinary ; Photosensitizing Agents - pharmacology ; Phototherapy - methods ; Science ; Tissue Distribution ; Triple Negative Breast Neoplasms - therapy ; Xenograft Model Antitumor Assays</subject><ispartof>Scientific reports, 2016-06, Vol.6 (1), p.27871-27871, Article 27871</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Jun 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-a1bd30d12adbd4641c9da804a55f130cf63dd65a3f0dac27f029dd0e91ab51663</citedby><cites>FETCH-LOGICAL-c504t-a1bd30d12adbd4641c9da804a55f130cf63dd65a3f0dac27f029dd0e91ab51663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908597/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908597/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,41119,42188,51575,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27302409$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Jiefu</creatorcontrib><creatorcontrib>Krishnamachary, Balaji</creatorcontrib><creatorcontrib>Mironchik, Yelena</creatorcontrib><creatorcontrib>Kobayashi, Hisataka</creatorcontrib><creatorcontrib>Bhujwalla, Zaver M.</creatorcontrib><title>Phototheranostics of CD44-positive cell populations in triple negative breast cancer</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44
high
/CD24
low
and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC.</description><subject>13/2</subject><subject>13/31</subject><subject>13/51</subject><subject>14/19</subject><subject>64/60</subject><subject>692/4017</subject><subject>692/4028/67/1059/602</subject><subject>692/4028/67/1347</subject><subject>692/4028/67/71</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Breast cancer</subject><subject>Cell Death - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hyaluronan Receptors - immunology</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Immunoconjugates - chemistry</subject><subject>Immunoconjugates - metabolism</subject><subject>Immunoconjugates - 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chemistry</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Breast cancer</topic><topic>Cell Death - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hyaluronan Receptors - immunology</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Immunoconjugates - chemistry</topic><topic>Immunoconjugates - metabolism</topic><topic>Immunoconjugates - pharmacology</topic><topic>Immunotherapy - methods</topic><topic>Irradiation</topic><topic>Mice, Inbred BALB C</topic><topic>Molecular Targeted Therapy - methods</topic><topic>multidisciplinary</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Phototherapy - methods</topic><topic>Science</topic><topic>Tissue Distribution</topic><topic>Triple Negative Breast Neoplasms - therapy</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jin, Jiefu</creatorcontrib><creatorcontrib>Krishnamachary, Balaji</creatorcontrib><creatorcontrib>Mironchik, Yelena</creatorcontrib><creatorcontrib>Kobayashi, Hisataka</creatorcontrib><creatorcontrib>Bhujwalla, Zaver M.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Jiefu</au><au>Krishnamachary, Balaji</au><au>Mironchik, Yelena</au><au>Kobayashi, Hisataka</au><au>Bhujwalla, Zaver M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phototheranostics of CD44-positive cell populations in triple negative breast cancer</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-06-15</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>27871</spage><epage>27871</epage><pages>27871-27871</pages><artnum>27871</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44
high
/CD24
low
and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27302409</pmid><doi>10.1038/srep27871</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/2 13/31 13/51 14/19 64/60 692/4017 692/4028/67/1059/602 692/4028/67/1347 692/4028/67/71 Animals Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - immunology Breast cancer Cell Death - drug effects Cell Line, Tumor Female Humanities and Social Sciences Humans Hyaluronan Receptors - immunology Hyaluronan Receptors - metabolism Immunoconjugates - chemistry Immunoconjugates - metabolism Immunoconjugates - pharmacology Immunotherapy - methods Irradiation Mice, Inbred BALB C Molecular Targeted Therapy - methods multidisciplinary Photosensitizing Agents - pharmacology Phototherapy - methods Science Tissue Distribution Triple Negative Breast Neoplasms - therapy Xenograft Model Antitumor Assays |
| title | Phototheranostics of CD44-positive cell populations in triple negative breast cancer |
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