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

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.06.050· OSTI ID:23136929

Chung, Heesung ^[1]; Jung, Hyejung ^[2]; Jho, Eek-hoon ^[3]; Multhaupt, Hinke A.B.; Couchman, John R. ^[4]; Oh, Eok-Soo ^[1]

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1. Department of Life Sciences, The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 03760 (Korea, Republic of)
2. Skin QC Institute of Dermatological Sciences, Seoul, 03759 (Korea, Republic of)
3. Department of Life Sciences, University of Seoul, Seoul, 02504 (Korea, Republic of)
4. Biotech Research & Innovation Center, University of Copenhagen, 2200, Copenhagen N (Denmark)

Highlights: • Human keratinocyte cells reduce the N-cadherin levels of co-cultured melanoma cells. • Cell-to-cell contact is necessary for this keratinocyte-mediated N-cadherin reduction. • Keratinocytes reduce intracellular calcium in co-cultured melanoma cells. • Keratinocytes reduce the expression of TRPCs in contacting melanoma cells. 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.

• OSTI ID: 23136929
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
MELANIN
MELANOMAS
RECEPTORS
SKIN