CD10 expressed by fibroblasts and melanoma cells degrades endothelin-1 secreted by human keratinocytes

Lining Xie, Yoichi Moroi, Masakazu Takahara, Gaku Tsuji, Junna Oba, Sayaka Hayashida, Satoshi Takeuchi, Baoen Shan, Hiroshi Uchi, Masutaka Furue

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)505-509
Number of pages5
JournalEuropean Journal of Dermatology
Issue number4
Publication statusPublished - 2011
Externally publishedYes


  • CD10
  • Endothelin-1
  • Fibroblast
  • Keratinocyte
  • Melanoma

ASJC Scopus subject areas

  • Dermatology


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