Abstract
Coculture of human melanocytes with keratinocytes upregulates CCN3, a matricellular protein critical to maintenance of normal homeostasis of melanocytes in the skin. CCN3 affects two fundamental features of melanocyte physiology: it inhibits melanocyte proliferation and stimulates their adhesion to the basement membrane. Here we report that expression of CCN3 is downregulated in advanced melanomas. Aggressive melanoma cell lines did not respond to treatment with CCN3 inducers, such as interleukin-1β (IL-1β), while less aggressive melanoma cell lines responded similarly to melanocytes. Immunostaining analyses revealed that CCN3 was present in melanoma cells close to the epidermal-dermal interface, but not in melanoma cells that had invaded deep into the dermis or had metastasized to lymph nodes. Contrary to our expectations, overexpression of CCN3 in 1205Lu metastatic melanoma cells did not affect their adhesion to collagen IV. However, CCN3 decreased the transcription and activation of matrix metalloproteinases and suppressed the invasion of 1205Lu melanoma cells. These results suggest that the lack of CCN3 in advanced melanoma cells contributes to their invasive phenotype. Whereas major matricellular proteins, such as osteopontin, tenascin or secreted protein acidic and rich in cysteine (SPARC), are strongly upregulated in melanoma cells; CCN3 is the first member of this family that is downregulated.
| Original language | English |
|---|---|
| Pages (from-to) | 2552-2560 |
| Number of pages | 9 |
| Journal | Oncogene |
| Volume | 27 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - Apr 17 2008 |
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Keywords
- CCN3
- Matricellular protein
- Matrix metalloproteinase
- Melanoma
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Downregulation of CCN3 expression as a potential mechanism for melanoma progression. / Fukunaga-Kalabis, M.; Martinez, G.; Telson, S. M.; Liu, Z. J.; Balint, K.; Juhasz, I.; Elder, D. E.; Perbal, B.; Herlyn, M.
In: Oncogene, Vol. 27, No. 18, 17.04.2008, p. 2552-2560.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Downregulation of CCN3 expression as a potential mechanism for melanoma progression
AU - Fukunaga-Kalabis, M.
AU - Martinez, G.
AU - Telson, S. M.
AU - Liu, Z. J.
AU - Balint, K.
AU - Juhasz, I.
AU - Elder, D. E.
AU - Perbal, B.
AU - Herlyn, M.
PY - 2008/4/17
Y1 - 2008/4/17
N2 - Coculture of human melanocytes with keratinocytes upregulates CCN3, a matricellular protein critical to maintenance of normal homeostasis of melanocytes in the skin. CCN3 affects two fundamental features of melanocyte physiology: it inhibits melanocyte proliferation and stimulates their adhesion to the basement membrane. Here we report that expression of CCN3 is downregulated in advanced melanomas. Aggressive melanoma cell lines did not respond to treatment with CCN3 inducers, such as interleukin-1β (IL-1β), while less aggressive melanoma cell lines responded similarly to melanocytes. Immunostaining analyses revealed that CCN3 was present in melanoma cells close to the epidermal-dermal interface, but not in melanoma cells that had invaded deep into the dermis or had metastasized to lymph nodes. Contrary to our expectations, overexpression of CCN3 in 1205Lu metastatic melanoma cells did not affect their adhesion to collagen IV. However, CCN3 decreased the transcription and activation of matrix metalloproteinases and suppressed the invasion of 1205Lu melanoma cells. These results suggest that the lack of CCN3 in advanced melanoma cells contributes to their invasive phenotype. Whereas major matricellular proteins, such as osteopontin, tenascin or secreted protein acidic and rich in cysteine (SPARC), are strongly upregulated in melanoma cells; CCN3 is the first member of this family that is downregulated.
AB - Coculture of human melanocytes with keratinocytes upregulates CCN3, a matricellular protein critical to maintenance of normal homeostasis of melanocytes in the skin. CCN3 affects two fundamental features of melanocyte physiology: it inhibits melanocyte proliferation and stimulates their adhesion to the basement membrane. Here we report that expression of CCN3 is downregulated in advanced melanomas. Aggressive melanoma cell lines did not respond to treatment with CCN3 inducers, such as interleukin-1β (IL-1β), while less aggressive melanoma cell lines responded similarly to melanocytes. Immunostaining analyses revealed that CCN3 was present in melanoma cells close to the epidermal-dermal interface, but not in melanoma cells that had invaded deep into the dermis or had metastasized to lymph nodes. Contrary to our expectations, overexpression of CCN3 in 1205Lu metastatic melanoma cells did not affect their adhesion to collagen IV. However, CCN3 decreased the transcription and activation of matrix metalloproteinases and suppressed the invasion of 1205Lu melanoma cells. These results suggest that the lack of CCN3 in advanced melanoma cells contributes to their invasive phenotype. Whereas major matricellular proteins, such as osteopontin, tenascin or secreted protein acidic and rich in cysteine (SPARC), are strongly upregulated in melanoma cells; CCN3 is the first member of this family that is downregulated.
KW - CCN3
KW - Matricellular protein
KW - Matrix metalloproteinase
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=42249083746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42249083746&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1210896
DO - 10.1038/sj.onc.1210896
M3 - Article
C2 - 17968313
AN - SCOPUS:42249083746
VL - 27
SP - 2552
EP - 2560
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 18
ER -