PMID- 14688525
OWN - NLM
STAT- MEDLINE
DCOM- 20040121
LR  - 20161124
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 76
IP  - 12
DP  - 2003 Dec 27
TI  - Mycophenolate mofetil increases adhesion capacity of tumor cells in vitro.
PG  - 1735-41
AB  - BACKGROUND: The immunosuppressive drug mycophenolate mofetil (MMF) reduces 
      expression of the heterophilic binding elements intercellular adhesion molecule-1 
      and vascular cell adhesion molecule-1 and thereby prevents attachment of 
      alloactivated leukocytes to donor endothelium. The authors speculated that MMF 
      might further diminish receptors of the immunoglobulin superfamily which, 
      however, act as homophilic binding elements. Because decrease of homophilic 
      adhesion receptors correlates with tumor dissemination and metastasis, MMF could 
      trigger development or recurrence of neoplastic tumors. METHODS: The authors 
      analyzed the influence of MMF on homotypic adhesion receptors and its consequence 
      for tumor cell attachment to an endothelial cell monolayer. Neuroblastoma (NB) 
      cells, which self-aggregate by means of the homophilic-binding element neural 
      cell adhesion molecule (NCAM), were used. Effects of MMF on the 140- and 180-kDa 
      NCAM isoforms were investigated quantitatively by flow cytometry, Western blot, 
      and reverse-transcriptase (RT) polymerase chain reaction (PCR). The relevance of 
      NCAM for tumor cell binding was proven by treating NB with NCAM antisense 
      oligonucleotides. RESULTS: MMF profoundly increased the number of adherent NB 
      cells, with a maximum effect at 0.1 microM, compared with controls. Decrease of 
      NCAM on the cell surface was detected by flow cytometry. Western blot and RT-PCR 
      demonstrated reduced protein and RNA levels of the 140- and 180-kDa isoforms. 
      Treatment of NB cells with NCAM antisense oligonucleotides showed that reduced 
      NCAM expression leads to enhanced tumor cell adhesion. CONCLUSIONS: MMF decreases 
      NCAM receptors, which is associated with enhanced tumor cell invasiveness. The 
      authors conclude that an MMF-based immunosuppressive regimen might increase the 
      risk of tumor metastasis if this process is predominantly conveyed by means of 
      homophilic adhesion proteins.
FAU - Blaheta, Roman A
AU  - Blaheta RA
AD  - Zentrum der Hygiene, Institut fur Medizinische Virologie, Johann Wolfgang 
      Goethe-Universitat, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. 
      blaheta@em.uni-frankfurt.de
FAU - Bogossian, Harilaos
AU  - Bogossian H
FAU - Beecken, Wolf-Dietrich
AU  - Beecken WD
FAU - Jonas, Dietger
AU  - Jonas D
FAU - Hasenberg, Christoph
AU  - Hasenberg C
FAU - Makarevic, Jasmina
AU  - Makarevic J
FAU - Ogbomo, Henry
AU  - Ogbomo H
FAU - Bechstein, Wolf O
AU  - Bechstein WO
FAU - Oppermann, Elsie
AU  - Oppermann E
FAU - Leckel, Kerstin
AU  - Leckel K
FAU - Cinatl, Jindrich Jr
AU  - Cinatl J Jr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (DNA Primers)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Base Sequence
MH  - Cell Adhesion/*drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - DNA Primers
MH  - Endothelium, Vascular/drug effects/*physiology
MH  - Humans
MH  - Kinetics
MH  - Mycophenolic Acid/*analogs & derivatives/*pharmacology
MH  - Neural Cell Adhesion Molecules/genetics
MH  - Polymerase Chain Reaction
MH  - Reproducibility of Results
MH  - Tumor Cells, Cultured
MH  - Umbilical Veins
EDAT- 2003/12/23 05:00
MHDA- 2004/01/22 05:00
CRDT- 2003/12/23 05:00
PHST- 2003/12/23 05:00 [pubmed]
PHST- 2004/01/22 05:00 [medline]
PHST- 2003/12/23 05:00 [entrez]
AID - 10.1097/01.TP.0000092004.83992.B2 [doi]
PST - ppublish
SO  - Transplantation. 2003 Dec 27;76(12):1735-41. doi: 
      10.1097/01.TP.0000092004.83992.B2.