Lipocalin-type prostaglandin D synthase as a marker for the proliferative potential of melanocyte-lineage cells in the human skin.
Melanocytes in the human epidermis actively produce and secrete various substances, thereby contributing to the maintenance of the skin homeostasis. Lipocalin-type prostaglandin D synthase (L-PGDS) that catalyzes the formation of prostaglandin D(2)  (PGD(2) ) may be one of such secreted molecules. Once secreted, L-PGDS functions as a transporter for lipophilic ligands, including all-trans retinoic acid (RA). L-PGDS, therefore, may possess pleiotropic functions in the skin through PGD(2)  and RA. We aimed to identify the cell types that express L-PGDS in human skin and to explore the role of L-PGDS in the growth potential of melanocyte-lineage cells. Immunohistochemical analysis for L-PGDS expression was performed with the tissue sections that were prepared from five malignant melanomas, six nevus cell nevi and one Spitz nevus. Normal skin tissues adjacent to the excised melanoma tissues were also analyzed. L-PGDS is expressed in epidermal melanocytes but its expression is undetectable in keratinocytes. Moreover, L-PGDS is undetectable in most benign nevus cells, which may reflect the marginally accelerated proliferation of nevus cells. In contrast, L-PGDS is overexpressed in malignant melanomas, although the frequency of L-PGDS-positive cells was variable (15-50%), depending on the specimens. Lastly, RNA interference analysis against human L-PGDS was performed with short interfering RNA. Knockdown of L-PGDS expression with short interfering RNA in cultured cells suggests that L-PGDS may restrict cell proliferation through RA. In conclusion, L-PGDS expression may contribute to the restricted proliferation of epidermal melanocytes, but conversely its overexpression may reflect the dysregulated proliferation of melanoma cells.
Department of Dermatology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Miwa
M
Shimanuki
Kazuhisa
K
Takeda
Masakazu
M
Kawaguchi
Tamio
T
Suzuki
Shigeki
S
Shibahara
D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D054834:Lipocalins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008297:Male; D008544:Melanocytes / Q000201:enzymology* / Q000473:pathology*; D008545:Melanoma / Q000201:enzymology / Q000473:pathology; D008875:Middle Aged; D009506:Nevus / Q000201:enzymology / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000201:enzymology*; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology
D054834:Lipocalins; D034741:RNA, Small Interfering; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase