Keratinocytes negatively regulate the N-cadherin levels of melanoma cells via contact-mediated calcium regulation

Heesung Chung, Hyejung Jung, Eek hoon Jho, Hinke A.B. Multhaupt, John R. Couchman, Eok Soo Oh

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

In human skin, melanocytes and their neighboring keratinocytes have a close functional interrelationship. Keratinocytes, which represent the prevalent cell type of human skin, regulate melanocytes through various mechanisms. Here, we use a keratinocyte and melanoma co-culture system to show for the first time that keratinocytes regulate the cell surface expression of N-cadherin through cell-cell contact. Compared to mono-cultured human melanoma A375 cells, which expressed high levels of N-cadherin, those co-cultured with the HaCaT human keratinocyte cell line showed reduced levels of N-cadherin. This reduction was most evident in areas of A375 cells that underwent cell-cell contact with the HaCaT cells, whereas HaCaT cell-derived extracellular matrix and conditioned medium both failed to reduce N-cadherin levels. The intracellular level of calcium in co-cultured A375 cells was lower than that in mono-cultured A375 cells, and treatment with a cell-permeant calcium chelator (BAPTA) reduced the N-cadherin level of mono-cultured A375 cells. Furthermore, co-culture with HaCaT cells reduced the expression levels of transient receptor potential cation channel (TRPC) 1, −3 and −6 in A375 cells, and siRNA-mediated multi-depletion of TRPC1, -3 and -6 reduced the N-cadherin level in these cells. Taken together, these data suggest that keratinocytes negatively regulate the N-cadherin levels of melanoma cells via cell-to-cell contact-mediated calcium regulation.

Original languageEnglish
Pages (from-to)615-620
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume503
Issue number2
DOIs
StatePublished - 5 Sep 2018

Keywords

  • Cell-cell interaction
  • Keratinocyte
  • Melanocyte
  • Melanoma
  • N-cadherin

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