Altered expression of P‐glycoprotein and cellular adhesion molecules on human multi‐drug‐resistant tumor cells does not affect their susceptibility to NK‐ and LAK‐mediated cytotoxicity
Drug resistance has been associated with resistance to NK‐ and LAK‐cell‐mediated cytotoxicity. We evaluated this issue in human cell lines, using multiple myeloma cells (8226) and 2 multi‐drug‐resistant (MDR) sublines selected using doxorubicin (8226/Dox40) and mitoxantrone (8226/MR40). In parallel,...
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| Veröffentlicht in: | International journal of cancer 1991-06, Vol.48 (4), p.562-567 |
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| container_title | International journal of cancer |
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| creator | Scheper, Rik J. Dalton, William S. Grogan, Thomas M. Schlosser, Arno Bellamy, William T. Taylor, Charles W. Scuderi, Phil Spier, Catherine |
| description | Drug resistance has been associated with resistance to NK‐ and LAK‐cell‐mediated cytotoxicity. We evaluated this issue in human cell lines, using multiple myeloma cells (8226) and 2 multi‐drug‐resistant (MDR) sublines selected using doxorubicin (8226/Dox40) and mitoxantrone (8226/MR40). In parallel, we studied the human breast carcinoma cell line series MCF7, MCF7/D40 and MCF7/Mitox. Unlike the sensitive parental cell lines, all 4 sublines display MDR‐patterns of resistance, with the P‐glycoprotein pump (P‐170) detected only in the doxorubicin‐selected sublines. Flow cytometric and immunocytochemical analyses showed expression of cellular adhesion molecules ICAM‐1 and LFA‐3, and MHC‐Class‐1 (MCF7/D40 only), to be decreased in the doxorubicin‐selected MDR‐sublines, whereas expression of CD56 (Leu 19) was strongly up‐regulated in 8226/Dox40. Lysis of P‐170‐positive MDR tumor cells by NK or LAK cells was, however, unaffected by these alterations, suggesting redundancy in effector: target‐cell adhesion pathways. Mitoxantrone‐selected tumor cells did not display P‐170, nor did they show altered expression of cellular adhesion molecules. Their susceptibility to NK or LAK cytolysis was also unimpaired as compared to the parental cell lines. Clinically, these results imply that immunotherapeutic modalities aiming at increased natural killer functions deserve full consideration even in patients who have become refractory to further cytostatic drug treatment. |
| doi_str_mv | 10.1002/ijc.2910480414 |
| format | Article |
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We evaluated this issue in human cell lines, using multiple myeloma cells (8226) and 2 multi‐drug‐resistant (MDR) sublines selected using doxorubicin (8226/Dox40) and mitoxantrone (8226/MR40). In parallel, we studied the human breast carcinoma cell line series MCF7, MCF7/D40 and MCF7/Mitox. Unlike the sensitive parental cell lines, all 4 sublines display MDR‐patterns of resistance, with the P‐glycoprotein pump (P‐170) detected only in the doxorubicin‐selected sublines. Flow cytometric and immunocytochemical analyses showed expression of cellular adhesion molecules ICAM‐1 and LFA‐3, and MHC‐Class‐1 (MCF7/D40 only), to be decreased in the doxorubicin‐selected MDR‐sublines, whereas expression of CD56 (Leu 19) was strongly up‐regulated in 8226/Dox40. Lysis of P‐170‐positive MDR tumor cells by NK or LAK cells was, however, unaffected by these alterations, suggesting redundancy in effector: target‐cell adhesion pathways. Mitoxantrone‐selected tumor cells did not display P‐170, nor did they show altered expression of cellular adhesion molecules. Their susceptibility to NK or LAK cytolysis was also unimpaired as compared to the parental cell lines. Clinically, these results imply that immunotherapeutic modalities aiming at increased natural killer functions deserve full consideration even in patients who have become refractory to further cytostatic drug treatment.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.2910480414</identifier><identifier>PMID: 1710609</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Antigens, CD - analysis ; Antigens, Differentiation, T-Lymphocyte - analysis ; Antigens, Surface - analysis ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Biological and medical sciences ; Breast Neoplasms ; CD56 Antigen ; CD58 Antigens ; Cell Adhesion ; Cell Adhesion Molecules - analysis ; Cell Line ; Cytotoxicity, Immunologic ; Doxorubicin - pharmacology ; Drug Resistance ; Histocompatibility Antigens Class I - analysis ; Histocompatibility Antigens Class II - analysis ; Host-tumor relations. Immunology. Biological markers ; Humans ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; killer cells ; Killer Cells, Lymphokine-Activated - immunology ; Killer Cells, Natural - immunology ; Kinetics ; Medical sciences ; Membrane Glycoproteins - analysis ; Membrane Glycoproteins - genetics ; Mitoxantrone - pharmacology ; Multiple Myeloma ; P-glycoprotein ; Tumors</subject><ispartof>International journal of cancer, 1991-06, Vol.48 (4), p.562-567</ispartof><rights>Copyright © 1991 Wiley‐Liss, Inc., A Wiley Company</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3154-6e521907bfa566f03f305509e870571cfbc4660d37fabbdc6d204875033d96b43</citedby><cites>FETCH-LOGICAL-c3154-6e521907bfa566f03f305509e870571cfbc4660d37fabbdc6d204875033d96b43</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%2Fijc.2910480414$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.2910480414$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4941251$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1710609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scheper, Rik J.</creatorcontrib><creatorcontrib>Dalton, William S.</creatorcontrib><creatorcontrib>Grogan, Thomas M.</creatorcontrib><creatorcontrib>Schlosser, Arno</creatorcontrib><creatorcontrib>Bellamy, William T.</creatorcontrib><creatorcontrib>Taylor, Charles W.</creatorcontrib><creatorcontrib>Scuderi, Phil</creatorcontrib><creatorcontrib>Spier, Catherine</creatorcontrib><title>Altered expression of P‐glycoprotein and cellular adhesion molecules on human multi‐drug‐resistant tumor cells does not affect their susceptibility to NK‐ and LAK‐mediated cytotoxicity</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Drug resistance has been associated with resistance to NK‐ and LAK‐cell‐mediated cytotoxicity. We evaluated this issue in human cell lines, using multiple myeloma cells (8226) and 2 multi‐drug‐resistant (MDR) sublines selected using doxorubicin (8226/Dox40) and mitoxantrone (8226/MR40). In parallel, we studied the human breast carcinoma cell line series MCF7, MCF7/D40 and MCF7/Mitox. Unlike the sensitive parental cell lines, all 4 sublines display MDR‐patterns of resistance, with the P‐glycoprotein pump (P‐170) detected only in the doxorubicin‐selected sublines. Flow cytometric and immunocytochemical analyses showed expression of cellular adhesion molecules ICAM‐1 and LFA‐3, and MHC‐Class‐1 (MCF7/D40 only), to be decreased in the doxorubicin‐selected MDR‐sublines, whereas expression of CD56 (Leu 19) was strongly up‐regulated in 8226/Dox40. Lysis of P‐170‐positive MDR tumor cells by NK or LAK cells was, however, unaffected by these alterations, suggesting redundancy in effector: target‐cell adhesion pathways. Mitoxantrone‐selected tumor cells did not display P‐170, nor did they show altered expression of cellular adhesion molecules. Their susceptibility to NK or LAK cytolysis was also unimpaired as compared to the parental cell lines. Clinically, these results imply that immunotherapeutic modalities aiming at increased natural killer functions deserve full consideration even in patients who have become refractory to further cytostatic drug treatment.</description><subject>Antigens, CD - analysis</subject><subject>Antigens, Differentiation, T-Lymphocyte - analysis</subject><subject>Antigens, Surface - analysis</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 1</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms</subject><subject>CD56 Antigen</subject><subject>CD58 Antigens</subject><subject>Cell Adhesion</subject><subject>Cell Adhesion Molecules - analysis</subject><subject>Cell Line</subject><subject>Cytotoxicity, Immunologic</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug Resistance</subject><subject>Histocompatibility Antigens Class I - analysis</subject><subject>Histocompatibility Antigens Class II - analysis</subject><subject>Host-tumor relations. Immunology. Biological markers</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intercellular Adhesion Molecule-1</subject><subject>killer cells</subject><subject>Killer Cells, Lymphokine-Activated - immunology</subject><subject>Killer Cells, Natural - immunology</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - analysis</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Mitoxantrone - pharmacology</subject><subject>Multiple Myeloma</subject><subject>P-glycoprotein</subject><subject>Tumors</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuO1DAQhiMEGpqBLTskLxC7NOUkdjrLVovHQAtYwDpy7PK0R07c-CEmO47AmTgKJ8H9EMNuVmW7vvqr_FdRPKewpADVa3Mjl1VHoVlBQ5sHxYJC15ZQUfawWGQAypbW_HHxJIQbAEoZNBfFBW0pcOgWxe-1jehREbzdewzBuIk4Tb78-fnr2s7S7b2LaCYiJkUkWpus8ESoHR7J0VmUyWIg-bJLo8hPyUaTq5VP1zlkTROimCKJaXT-qBGIcrlkcpEIrVHm3A6NJyEFiftoBmNNnEl05NPHLHHsvV0fjiMqI2KeVs7RRXdrZAafFo-0sAGfneNl8e3tm6-b9-X287urzXpbypqypuTIKtpBO2jBONdQ6xoYgw5XLbCWSj3IhnNQdavFMCjJVZVNbRnUter40NSXxauTbvbke8IQ-9GEw3_EhC6FfpUdrWhF7wUphxWraZvB5QmU3oXgUfd7b0bh555Cf9hun7fb3203F7w4K6che3GHn9aZ8y_PeRGksNqLSZrwD2u6hlbsMGB3wn4Yi_M9TfurD5v_RvgL6C7GTg</recordid><startdate>19910619</startdate><enddate>19910619</enddate><creator>Scheper, Rik J.</creator><creator>Dalton, William S.</creator><creator>Grogan, Thomas M.</creator><creator>Schlosser, Arno</creator><creator>Bellamy, William T.</creator><creator>Taylor, Charles W.</creator><creator>Scuderi, Phil</creator><creator>Spier, Catherine</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>IQODW</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><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19910619</creationdate><title>Altered expression of P‐glycoprotein and cellular adhesion molecules on human multi‐drug‐resistant tumor cells does not affect their susceptibility to NK‐ and LAK‐mediated cytotoxicity</title><author>Scheper, Rik J. ; Dalton, William S. ; Grogan, Thomas M. ; Schlosser, Arno ; Bellamy, William T. ; Taylor, Charles W. ; Scuderi, Phil ; Spier, Catherine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3154-6e521907bfa566f03f305509e870571cfbc4660d37fabbdc6d204875033d96b43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Antigens, CD - analysis</topic><topic>Antigens, Differentiation, T-Lymphocyte - analysis</topic><topic>Antigens, Surface - analysis</topic><topic>ATP Binding Cassette Transporter, Subfamily B, Member 1</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms</topic><topic>CD56 Antigen</topic><topic>CD58 Antigens</topic><topic>Cell Adhesion</topic><topic>Cell Adhesion Molecules - analysis</topic><topic>Cell Line</topic><topic>Cytotoxicity, Immunologic</topic><topic>Doxorubicin - pharmacology</topic><topic>Drug Resistance</topic><topic>Histocompatibility Antigens Class I - analysis</topic><topic>Histocompatibility Antigens Class II - analysis</topic><topic>Host-tumor relations. Immunology. Biological markers</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intercellular Adhesion Molecule-1</topic><topic>killer cells</topic><topic>Killer Cells, Lymphokine-Activated - immunology</topic><topic>Killer Cells, Natural - immunology</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - analysis</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Mitoxantrone - pharmacology</topic><topic>Multiple Myeloma</topic><topic>P-glycoprotein</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scheper, Rik J.</creatorcontrib><creatorcontrib>Dalton, William S.</creatorcontrib><creatorcontrib>Grogan, Thomas M.</creatorcontrib><creatorcontrib>Schlosser, Arno</creatorcontrib><creatorcontrib>Bellamy, William T.</creatorcontrib><creatorcontrib>Taylor, Charles W.</creatorcontrib><creatorcontrib>Scuderi, Phil</creatorcontrib><creatorcontrib>Spier, Catherine</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scheper, Rik J.</au><au>Dalton, William S.</au><au>Grogan, Thomas M.</au><au>Schlosser, Arno</au><au>Bellamy, William T.</au><au>Taylor, Charles W.</au><au>Scuderi, Phil</au><au>Spier, Catherine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered expression of P‐glycoprotein and cellular adhesion molecules on human multi‐drug‐resistant tumor cells does not affect their susceptibility to NK‐ and LAK‐mediated cytotoxicity</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>1991-06-19</date><risdate>1991</risdate><volume>48</volume><issue>4</issue><spage>562</spage><epage>567</epage><pages>562-567</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>Drug resistance has been associated with resistance to NK‐ and LAK‐cell‐mediated cytotoxicity. We evaluated this issue in human cell lines, using multiple myeloma cells (8226) and 2 multi‐drug‐resistant (MDR) sublines selected using doxorubicin (8226/Dox40) and mitoxantrone (8226/MR40). In parallel, we studied the human breast carcinoma cell line series MCF7, MCF7/D40 and MCF7/Mitox. Unlike the sensitive parental cell lines, all 4 sublines display MDR‐patterns of resistance, with the P‐glycoprotein pump (P‐170) detected only in the doxorubicin‐selected sublines. Flow cytometric and immunocytochemical analyses showed expression of cellular adhesion molecules ICAM‐1 and LFA‐3, and MHC‐Class‐1 (MCF7/D40 only), to be decreased in the doxorubicin‐selected MDR‐sublines, whereas expression of CD56 (Leu 19) was strongly up‐regulated in 8226/Dox40. Lysis of P‐170‐positive MDR tumor cells by NK or LAK cells was, however, unaffected by these alterations, suggesting redundancy in effector: target‐cell adhesion pathways. Mitoxantrone‐selected tumor cells did not display P‐170, nor did they show altered expression of cellular adhesion molecules. Their susceptibility to NK or LAK cytolysis was also unimpaired as compared to the parental cell lines. Clinically, these results imply that immunotherapeutic modalities aiming at increased natural killer functions deserve full consideration even in patients who have become refractory to further cytostatic drug treatment.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>1710609</pmid><doi>10.1002/ijc.2910480414</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0020-7136 |
| ispartof | International journal of cancer, 1991-06, Vol.48 (4), p.562-567 |
| issn | 0020-7136 1097-0215 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80602121 |
| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Antigens, CD - analysis Antigens, Differentiation, T-Lymphocyte - analysis Antigens, Surface - analysis ATP Binding Cassette Transporter, Subfamily B, Member 1 Biological and medical sciences Breast Neoplasms CD56 Antigen CD58 Antigens Cell Adhesion Cell Adhesion Molecules - analysis Cell Line Cytotoxicity, Immunologic Doxorubicin - pharmacology Drug Resistance Histocompatibility Antigens Class I - analysis Histocompatibility Antigens Class II - analysis Host-tumor relations. Immunology. Biological markers Humans Immunohistochemistry Intercellular Adhesion Molecule-1 killer cells Killer Cells, Lymphokine-Activated - immunology Killer Cells, Natural - immunology Kinetics Medical sciences Membrane Glycoproteins - analysis Membrane Glycoproteins - genetics Mitoxantrone - pharmacology Multiple Myeloma P-glycoprotein Tumors |
| title | Altered expression of P‐glycoprotein and cellular adhesion molecules on human multi‐drug‐resistant tumor cells does not affect their susceptibility to NK‐ and LAK‐mediated cytotoxicity |
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