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Expression and functional role of CRIPTO-1 in cutaneous melanoma
A De Luca1, L Lamura, L Strizzi
1Cell Biology and Biotherapy Unit, Research Department, INT-Fondazione Pascale, Naples 80131, Italy.
British Journal of Cancer
|August 25, 2011
Summary
The growth factor CRIPTO-1 (CR-1) is expressed in a significant portion of cutaneous melanomas. CR-1 promotes melanoma cell invasion and proliferation, suggesting it is a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- CRIPTO-1 (CR-1) is implicated in the pathogenesis and progression of various human carcinomas.
- This study investigates the expression and functional significance of CR-1 in cutaneous melanoma.
Purpose of the Study:
- To determine the expression levels of CR-1 in primary cutaneous melanomas and melanoma cell lines.
- To elucidate the functional role of CR-1 in melanoma cell invasion and proliferation.
Main Methods:
- Immunohistochemistry, western blotting, flow cytometry, and real-time PCR were used to assess CR-1 expression.
- Invasion assays were conducted using Matrigel-coated Boyden chambers.
- Melanoma cells were treated with recombinant CR-1, ALK4 inhibitor SB-431542, c-Src inhibitor saracatinib, and anti-CR-1 siRNAs.
Main Results:
- CR-1 expression was detected in 16 of 37 primary melanomas and 12 of 21 melanoma cell lines.
- Recombinant CR-1 activated c-Src and Smad signaling, enhancing melanoma cell invasion.
- Inhibition of CR-1 or its downstream signaling pathways (ALK4, c-Src) significantly reduced melanoma cell growth and invasion.
Conclusions:
- A substantial fraction of cutaneous melanomas express CR-1.
- CR-1 plays a significant role in melanoma cell invasion and proliferation.
- CR-1 represents a potential therapeutic target for cutaneous melanoma.
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