1
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 is associated with reduced 25-hydroxyvitamin D serum levels B. Nu ¨ rnberg 1 , D. Schadendorf 2 , B. Ga ¨ rtner 3 , C. Pfo ¨ hler 1 , W. Herrmann 4 , W. Tilgen 1 and J. Reichrath 1 1 Department of Dermatology, The Saarland University Hospital, Homburg, Germany; 2 Department of Dermatology, Medical Faculty of Mannheim, Germany; 3 Institute of Virology, The Saarland University Hospital, Homburg, Germany; 4 Department 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: olfactory neurons with MHC-like peptide binding properties’ Professor Dr Trese Leinders-Zufall Institute 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

Guest lecture: ‘Love at first smell: olfactory neurons with MHC-like peptide binding properties’

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Page 1: Guest lecture: ‘Love at first smell: olfactory neurons with MHC-like peptide binding properties’

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