TY - JOUR
T1 - CD10 expressed by fibroblasts and melanoma cells degrades endothelin-1 secreted by human keratinocytes
AU - Xie, Lining
AU - Moroi, Yoichi
AU - Takahara, Masakazu
AU - Tsuji, Gaku
AU - Oba, Junna
AU - Hayashida, Sayaka
AU - Takeuchi, Satoshi
AU - Shan, Baoen
AU - Uchi, Hiroshi
AU - Furue, Masutaka
PY - 2011
Y1 - 2011
N2 - Endothelin-1 (ET-1) is a potent multifunctional peptide linked to wound healing, pigmentation, carcinogenesis, and fibrosclerotic processes in the skin. Whereas ET-1 was thought to be digested by receptor-mediated endocytosis, it is also reported to be biochemically degraded by the neutral endopeptidase CD10 using kidney homogenates. Although keratinocytes (KC) and fibroblasts (Fb) are sources of both ET-1 and CD10, respectively, there is no report investigating the direct association betweenCD10expression and its function in relation toET-1 degradation in the skin. CD10 expression in melanoma cells is associated with clinical prognosis, suggesting an important role in the invasive and metastatic potential of melanoma cells. Here, cultured KC produced much higher amounts of ET-1 than did cultured Fb or melanoma cells. In contrast, KC and A375 melanoma cells did not express CD10, while Fb, SK-MEL-28 and G361 melanoma cells constitutively expressed CD10. KC-derived ET-1was down-modulated by both CD10-positive Fb and CD10-positive melanoma cells, and the inhibition was partially reversed under substitution conditions using CD10-knockdown Fb or CD10-knockdown melanoma cells. This indicates that CD10 on cultured Fb and melanoma cells is biochemically active in the degradation or down-modulation of ET-1 secreted from KC. These findings may lead to better understanding of skin homeostasis and of the malignant potential of melanoma.
AB - Endothelin-1 (ET-1) is a potent multifunctional peptide linked to wound healing, pigmentation, carcinogenesis, and fibrosclerotic processes in the skin. Whereas ET-1 was thought to be digested by receptor-mediated endocytosis, it is also reported to be biochemically degraded by the neutral endopeptidase CD10 using kidney homogenates. Although keratinocytes (KC) and fibroblasts (Fb) are sources of both ET-1 and CD10, respectively, there is no report investigating the direct association betweenCD10expression and its function in relation toET-1 degradation in the skin. CD10 expression in melanoma cells is associated with clinical prognosis, suggesting an important role in the invasive and metastatic potential of melanoma cells. Here, cultured KC produced much higher amounts of ET-1 than did cultured Fb or melanoma cells. In contrast, KC and A375 melanoma cells did not express CD10, while Fb, SK-MEL-28 and G361 melanoma cells constitutively expressed CD10. KC-derived ET-1was down-modulated by both CD10-positive Fb and CD10-positive melanoma cells, and the inhibition was partially reversed under substitution conditions using CD10-knockdown Fb or CD10-knockdown melanoma cells. This indicates that CD10 on cultured Fb and melanoma cells is biochemically active in the degradation or down-modulation of ET-1 secreted from KC. These findings may lead to better understanding of skin homeostasis and of the malignant potential of melanoma.
KW - CD10
KW - Endothelin-1
KW - Fibroblast
KW - Keratinocyte
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=80053003943&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053003943&partnerID=8YFLogxK
U2 - 10.1684/ejd.2011.1371
DO - 10.1684/ejd.2011.1371
M3 - Article
C2 - 21616752
AN - SCOPUS:80053003943
SN - 1167-1122
VL - 21
SP - 505
EP - 509
JO - European Journal of Dermatology
JF - European Journal of Dermatology
IS - 4
ER -