PMID- 22745469
OWN - NLM
STAT- MEDLINE
DCOM- 20120917
LR  - 20181201
IS  - 1460-2105 (Electronic)
IS  - 0027-8874 (Linking)
VI  - 104
IP  - 13
DP  - 2012 Jul 3
TI  - Role of interleukin 16 in multiple myeloma.
PG  - 1005-20
LID - 10.1093/jnci/djs257 [doi]
AB  - BACKGROUND: Multiple myeloma is a malignancy characterized by the expansion of a 
      plasma cell clone that localizes to the human bone marrow. Myeloma cells and bone 
      marrow stromal cells produce soluble factors that promote the survival and 
      progression of multiple myeloma. Interleukin 16 (IL-16) is involved in regulating 
      the migration and proliferation of normal leukocytes. However, the role of IL-16 
      in human cancers, including multiple myeloma, is unclear. METHODS: We 
      investigated IL-16 expression in cell lines (n = 10) and in the bone marrow of 
      myeloma patients (n = 62) and healthy bone marrow donors (n = 12) by quantitative 
      reverse transcription-polymerase chain reaction, immunoblot analysis, 
      enzyme-linked immunosorbent assay, flow cytometry, and immunohistochemistry. 
      Transfection of two human multiple myeloma cell lines with small interfering RNAs 
      was used to examine the effect of IL-16 gene silencing on apoptosis by flow 
      cytometry, on proliferation by bromodeoxyuridine incorporation, and on colony 
      formation. Protein neutralization assays were performed by treating multiple 
      myeloma cells with a monoclonal antibody against the carboxyl-terminal fragment 
      of IL-16. All statistical tests were two-sided. RESULTS: IL-16 was strongly 
      overexpressed in the bone marrow of myeloma patients compared with healthy 
      donors. Myeloma cell lines as well as primary tumor cells from myeloma patients 
      constitutively expressed IL-16 and its receptors CD4 and/or CD9 and spontaneously 
      secreted soluble IL-16. Silencing of IL-16 reduced the proliferative activity of 
      myeloma cells by approximately 80% compared with untreated cells (mean relative 
      proliferative activity IL-16 siRNA vs untransfected cells, EJM cells: 20.1%, 95% 
      confidence interval [CI] = 14.3% to 26.0%, P = .03; KMS-12-BM cells: 22.8%, 95% 
      CI = 5.5% to 40.0%, P = .04), and addition of a recombinant carboxyl-terminal 
      IL-16 peptide reversed that effect. A monoclonal antibody directed against IL-16 
      or its receptors had a comparably strong growth-inhibiting effect on the tumor 
      cells. CONCLUSIONS: IL-16 is an important growth-promoting factor in multiple 
      myeloma and a candidate for novel diagnostic, prognostic, and therapeutic 
      applications for this incurable human malignancy.
FAU - Atanackovic, Djordje
AU  - Atanackovic D
AD  - Department of Medicine II, Oncology/Hematology/Stem Cell Transplantation, 
      University Cancer Center Hamburg (Hubertus Wald Tumorzentrum), University Medical 
      Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany. 
      d.atanackovic@uke.uni-hamburg.de
FAU - Hildebrandt, York
AU  - Hildebrandt Y
FAU - Templin, Julia
AU  - Templin J
FAU - Cao, Yanran
AU  - Cao Y
FAU - Keller, Christiane
AU  - Keller C
FAU - Panse, Jens
AU  - Panse J
FAU - Meyer, Sabrina
AU  - Meyer S
FAU - Reinhard, Henrike
AU  - Reinhard H
FAU - Bartels, Katrin
AU  - Bartels K
FAU - Lajmi, Nesrine
AU  - Lajmi N
FAU - Sezer, Orhan
AU  - Sezer O
FAU - Zander, Axel R
AU  - Zander AR
FAU - Marx, Andreas H
AU  - Marx AH
FAU - Uhlig, Ria
AU  - Uhlig R
FAU - Zustin, Jozef
AU  - Zustin J
FAU - Bokemeyer, Carsten
AU  - Bokemeyer C
FAU - Kroger, Nicolaus
AU  - Kroger N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120628
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - 0 (CD4 Antigens)
RN  - 0 (CD9 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tetraspanin 29)
SB  - IM
CIN - J Natl Cancer Inst. 2012 Jul 3;104(13):964-5. PMID: 22745468
MH  - Adult
MH  - Aged
MH  - Apoptosis
MH  - Bone Marrow Cells/*metabolism
MH  - CD4 Antigens/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Silencing
MH  - Humans
MH  - Immunohistochemistry
MH  - Interleukin-6/*genetics/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*metabolism
MH  - Neoplastic Stem Cells/metabolism
MH  - Plasma Cells/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tetraspanin 29/metabolism
MH  - Up-Regulation
EDAT- 2012/06/30 06:00
MHDA- 2012/09/18 06:00
CRDT- 2012/06/30 06:00
PHST- 2012/06/30 06:00 [entrez]
PHST- 2012/06/30 06:00 [pubmed]
PHST- 2012/09/18 06:00 [medline]
AID - djs257 [pii]
AID - 10.1093/jnci/djs257 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 2012 Jul 3;104(13):1005-20. doi: 10.1093/jnci/djs257. Epub 
      2012 Jun 28.