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The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells.
Cancer Res. 2007 Sep 15; 67(18):8444-9.CR

Abstract

Recent evidence suggests a role for natural killer (NK) cells in the control of multiple myeloma. We show that expression of the NK cell receptor DNAM-1 (CD226) is reduced on CD56(dim) NK cells from myeloma patients with active disease compared with patients in remission and healthy controls. This suggested that this receptor might play a role in NK-myeloma interactions. The DNAM-1 ligands Nectin-2 (CD112) and the poliovirus receptor (PVR; CD155) were expressed by most patient myeloma samples analyzed. NK killing of patient-derived myelomas expressing PVR and/or Nectin-2 was DNAM-1 dependent, revealing a functional role for DNAM-1 in myeloma cell killing. In myeloma cell lines, cell surface expression of PVR was associated with low levels of NKG2D ligands, whereas cells expressing high levels of NKG2D ligands did not express PVR protein or mRNA. Furthermore, NK cell-mediated killing of myeloma cell lines was dependent on either DNAM-1 or NKG2D but not both molecules. In contrast, the natural cytotoxicity receptor NKp46 was required for the killing of all myeloma cell lines analyzed. Thus, DNAM-1 is important in the NK cell-mediated killing of myeloma cells expressing the cognate ligands. The importance of NKp46, NKG2D, and DNAM-1 in myeloma killing mirrors the differential expression of NK cell ligands by myeloma cells, reflecting immune selection during myeloma disease progression.

Authors+Show Affiliations

Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, St. James's University Hospital, Leeds, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17875681

Citation

El-Sherbiny, Yasser M., et al. "The Requirement for DNAM-1, NKG2D, and NKp46 in the Natural Killer Cell-mediated Killing of Myeloma Cells." Cancer Research, vol. 67, no. 18, 2007, pp. 8444-9.
El-Sherbiny YM, Meade JL, Holmes TD, et al. The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells. Cancer Res. 2007;67(18):8444-9.
El-Sherbiny, Y. M., Meade, J. L., Holmes, T. D., McGonagle, D., Mackie, S. L., Morgan, A. W., Cook, G., Feyler, S., Richards, S. J., Davies, F. E., Morgan, G. J., & Cook, G. P. (2007). The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells. Cancer Research, 67(18), 8444-9.
El-Sherbiny YM, et al. The Requirement for DNAM-1, NKG2D, and NKp46 in the Natural Killer Cell-mediated Killing of Myeloma Cells. Cancer Res. 2007 Sep 15;67(18):8444-9. PubMed PMID: 17875681.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells. AU - El-Sherbiny,Yasser M, AU - Meade,Josephine L, AU - Holmes,Tim D, AU - McGonagle,Dennis, AU - Mackie,Sarah L, AU - Morgan,Ann W, AU - Cook,Gordon, AU - Feyler,Sylvia, AU - Richards,Stephen J, AU - Davies,Faith E, AU - Morgan,Gareth J, AU - Cook,Graham P, PY - 2007/9/19/pubmed PY - 2007/12/6/medline PY - 2007/9/19/entrez SP - 8444 EP - 9 JF - Cancer research JO - Cancer Res. VL - 67 IS - 18 N2 - Recent evidence suggests a role for natural killer (NK) cells in the control of multiple myeloma. We show that expression of the NK cell receptor DNAM-1 (CD226) is reduced on CD56(dim) NK cells from myeloma patients with active disease compared with patients in remission and healthy controls. This suggested that this receptor might play a role in NK-myeloma interactions. The DNAM-1 ligands Nectin-2 (CD112) and the poliovirus receptor (PVR; CD155) were expressed by most patient myeloma samples analyzed. NK killing of patient-derived myelomas expressing PVR and/or Nectin-2 was DNAM-1 dependent, revealing a functional role for DNAM-1 in myeloma cell killing. In myeloma cell lines, cell surface expression of PVR was associated with low levels of NKG2D ligands, whereas cells expressing high levels of NKG2D ligands did not express PVR protein or mRNA. Furthermore, NK cell-mediated killing of myeloma cell lines was dependent on either DNAM-1 or NKG2D but not both molecules. In contrast, the natural cytotoxicity receptor NKp46 was required for the killing of all myeloma cell lines analyzed. Thus, DNAM-1 is important in the NK cell-mediated killing of myeloma cells expressing the cognate ligands. The importance of NKp46, NKG2D, and DNAM-1 in myeloma killing mirrors the differential expression of NK cell ligands by myeloma cells, reflecting immune selection during myeloma disease progression. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/17875681/The_requirement_for_DNAM_1_NKG2D_and_NKp46_in_the_natural_killer_cell_mediated_killing_of_myeloma_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17875681 DB - PRIME DP - Unbound Medicine ER -