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

Rik J. Scheper, William S. Dalton, Thomas M. Grogan, Arno Schlosser, William T. Bellamy, Charles W. Taylor, Phil Scuderi, Catherine S Perry

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)562-567
Number of pages6
JournalInternational Journal of Cancer
Volume48
Issue number4
DOIs
StatePublished - 1991

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Cell Line
Neoplasms
Lymphokine-Activated Killer Cells
Mitoxantrone
Cytostatic Agents
Multiple Myeloma
Drug Resistance
Natural Killer Cells
Doxorubicin
Breast Neoplasms
Therapeutics
chlorbenside

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

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. / Scheper, Rik J.; Dalton, William S.; Grogan, Thomas M.; Schlosser, Arno; Bellamy, William T.; Taylor, Charles W.; Scuderi, Phil; Perry, Catherine S.

In: International Journal of Cancer, Vol. 48, No. 4, 1991, p. 562-567.

Research output: Contribution to journalArticle

Scheper, Rik J. ; Dalton, William S. ; Grogan, Thomas M. ; Schlosser, Arno ; Bellamy, William T. ; Taylor, Charles W. ; Scuderi, Phil ; Perry, Catherine S. / 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. In: International Journal of Cancer. 1991 ; Vol. 48, No. 4. pp. 562-567.
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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.",
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