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expression of corresponding nuclear receptors in MeWo
cells? (III) Can we find hinds for a cross-regulation of
PPAR- and VDR-signaling pathways in MeWo cells?
Using real time PCR, we have characterized expression of
PPARa, -d ,-c and VDR in the melanoma cell line MeWo.
We show that PPARa and -d are much stronger
expressed in melanoma cell lines than PPARc. We dem-
onstrate antiproliferative effects of various PPAR-ligands
and/or 1,25(OH)2D3 on melanoma cell lines. PPAR-
ligands and/or 1,25(OH)2D3 significantly modulate
PPAR- and VDR-Expression. This suggests that PPAR-
and VDR-signaling pathways are interconnected by reci-
procal effects of the activated receptors. In conclusion,
our data support the concept that PPARs may be of
importance for pathogenesis, progression, and therapy of
malignant melanoma.
5
Progression of malignant melanoma isassociated with reduced 25-hydroxyvitamin Dserum levelsB. Nurnberg1, D. Schadendorf2, B. Gartner3, C. Pfohler1,W. Herrmann4, W. Tilgen1 and J. Reichrath1
1Department of Dermatology, The Saarland University Hospital,
Homburg, Germany; 2Department of Dermatology, Medical Faculty of
Mannheim, Germany; 3Institute of Virology, The Saarland University
Hospital, Homburg, Germany; 4Department of Clinical Chemistry and
Laboratory Medicine, The Saarland University Hospital, Homburg,
Germany
Solar UV-exposure, particularly intensive short-time and
recreational sun exposure, is considered to be the major
etiologic factor for melanoma. But on the other hand
90% of all requisite vitamin D has to be formed in the
skin through the action of the sun – a serious problem
due to the fact that new scientific findings convincingly
demonstrate vitamin D deficiency to be associated with a
variety of severe diseases including various types of cancer
(e.g. colon, prostate and breast cancer). According to
recent reports sun exposure is associated with a relatively
favorable prognosis and increased survival rate in various
malignancies, including malignant melanoma. It has been
speculated that these findings were related to UV expo-
sure-induced relatively high serum levels of vitamin D
which may lead to a more favorable course of melanoma.
To prove this hypothesis the present study aimed to
correlate the serum level of 25-hydroxyvitamin D (which
represents the readily measurable ‘storage’ precursor form
of vitamin D) with tumor thickness at time of diagnosis
and course of disease in patients with melanoma. The
study population consisted of 212 patients with histologi-
cally proven cutaneous melanomas of different stages:
stage I (n = 50); stage II (n = 20); stage III (n = 20);
stage IV (n = 122). Basal 25-hydroxyvitamin D levels were
analyzed (DiaSorin LIAISON 25-OH Vitamin D-Assay) in
those patients and compared with a control group
(n = 80). Additionally, each participant was requested to
fill out a questionnaire about the history of sun exposure.
Interestingly, basal 25-hydroxyvitamin D levels were lower
in melanoma patients as compared to the control group,
although this difference was statistically not significant.
Moreover, progression of malignant melanoma was associ-
ated with statistically significantly reduced 25-hydroxyvita-
min D serum levels. In conclusion, our findings add to
the growing body of evidence that 25-hydroxyvitamin D
serum levels may be of importance for pathogenesis and
progression of malignant melanoma.
6
Guest lecture: ‘Love at first smell: olfactoryneurons with MHC-like peptide bindingproperties’Professor Dr Trese Leinders-ZufallInstitute of Physiology, School of Medicine, University of Saarland,
Homburg/Saar, Germany
Social interactions, such as finding and identifying a mate,
often rely on the ability to sense molecular cues carrying
information about genetic relationship and individuality.
Genes residing in the major histocompatibility complex
(MHC) influence body odor and reproductive decisions in
many vertebrate species. In mice, the olfactory sensory neu-
rons respond to small peptides that also serve as ligands of
MHC molecules. These MHC peptides constitute a large
family of social recognition signals detected by sensory
neurons in at least two olfactory subsystems, the mamma-
lian main and the accessory olfactory systems. Interestingly,
MHC peptides can be detected at extremely low concentra-
tions, in the picomolar range, suggesting that specific
mechanisms have evolved in the mammalian nose to assess
the structural diversity of these molecules. Our results sug-
gest a novel mechanism explaining the enigmatic influence
of MHC genotypic diversity on behavior. This discovery
proposes a mechanism by which animals identify other
individuals of their species based on the unique structures
of their immune-system proteins.
Abstracts
ª 2008 The Authors
Journal compilation ª 2008 Blackwell Munksgaard, Experimental Dermatology, 17, 624–632 627