Gene expression profiling of human melanoma cell lines with distinct metastatic potential identifies new progression markers.
BACKGROUND
Identification of markers associated with melanoma progression is crucial to identify new prognostic and/or therapeutic targets.


METHODS
By using DNA microarrays, two human melanoma cell lines, M4Be and Tw12, derived from the same tumor, but with different metastatic potential, were profiled. Western blot of cell lines, immunohistochemistry on melanoma biopsies and in silico analyses validated and extended our results.


RESULTS
Thirty-six clones were differentially-expressed between the two cell lines, representing 33 named genes and 2 expressed sequence tags. The most up-regulated gene in the strongly metastatic clone Tw12 was CD10. Protein analysis with anti-CD1O antibody confirmed this finding in cell lines and clinical samples with expression being more frequent in metastatic compared to primary tumors. Many up-regulated genes were involved in angiogenesis, invasion, growth and apoptosis. Down-regulated genes included tumor suppressor genes and those were involved in differentiation.


CONCLUSIONS
We identified several genes the expression of which is associated with metastatic progression in human melanoma cells. Although further analyses are warranted to clarify their exact role in tumor progression, they might lead to new prognostic markers and/or molecular therapeutic targets in metastatic melanoma.
Bertucci
François
F
Departments of Medical Oncology, UMR599 INSERM, Institut Paoli Calmettes, Marseille, France. bertuccif@marseille.fnclcc.fr
Pages
Cécile
C
Finetti
Pascal
P
Rochaix
Philippe
P
Lamant
Laurence
L
Devilard
Elizabeth
E
Nguyen
Cathy
C
Houlgatte
Rémi
R
Birnbaum
Daniel
D
Xerri
Luc
L
Brousset
Pierre
P
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015260:Neprilysin / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
D014408:Biomarkers, Tumor; D015260:Neprilysin