Gene expression profiles of human melanoma cells with different invasive potential reveal TSPAN8 as a novel mediator of invasion

Metastatic melanoma requires early detection, being treatment resistant. However, the earliest events of melanoma metastasis, and especially of dermal invasion, remain ill defined. Gene expression profiles of two clonal subpopulations, selected from the same human melanoma cell line, but differing i...

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Bibliographic Details
Published in:British journal of cancer 2011-01, Vol.104 (1), p.155-165
Main Authors: BERTHIER-VERGNES, O, EL KHARBILI, M, DE LA FOUCHARDIERE, A, POINTECOUTEAU, T, VERRANDO, P, WIERINCKX, A, LACHUER, J, LE NAOUR, F, LAMARTINE, J
Format: Article
Language:English
Subjects:
Antigens, Neoplasm
Antigens, Neoplasm - genetics
Antigens, Neoplasm - metabolism
Apoptosis
Biochemistry, Molecular Biology
Biological and medical sciences
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Blotting, Western
Cancer research
Cell Movement
Cell Proliferation
Cloning
Dermatology
Flow Cytometry
Gene expression
Gene Expression Profiling
Humans
Immunoenzyme Techniques
Life Sciences
Lymphatic Metastasis
Medical research
Medical sciences
Melanocytes
Melanocytes - metabolism
Melanoma
Melanoma - genetics
Melanoma - metabolism
Melanoma - pathology
Membrane Glycoproteins
Membrane Glycoproteins - antagonists & inhibitors
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Metastasis
Molecular Diagnostics
Neoplasm Invasiveness
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger
RNA, Messenger - genetics
RNA, Small Interfering
RNA, Small Interfering - genetics
Skin Neoplasms
Skin Neoplasms - genetics
Skin Neoplasms - metabolism
Skin Neoplasms - pathology
Spheroids, Cellular
Spheroids, Cellular - metabolism
Spheroids, Cellular - pathology
Tetraspanins
Tumor Cells, Cultured
Tumor Markers, Biological
Tumors
Tumors of the skin and soft tissue. Premalignant lesions
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Summary:Metastatic melanoma requires early detection, being treatment resistant. However, the earliest events of melanoma metastasis, and especially of dermal invasion, remain ill defined. Gene expression profiles of two clonal subpopulations, selected from the same human melanoma cell line, but differing in ability to cross the dermal-epidermal junction in skin reconstructs, were compared by oligonucleotide microarray. Of 26 496 cDNA probes, 461 were differentially expressed (>2-fold; P< 0.001), only 71 genes being upregulated in invasive cells. Among them, TSPAN8, a tetraspanin not yet described in melanoma, was upregulated at mRNA and protein levels in melanoma cells from the invasive clone, as assessed by RT-PCR, flow cytometry and western blot analysis. Interestingly, TSPAN8 was the only tetraspanin in which overexpression correlated with invasive phenotype. Flow cytometry of well-defined melanoma cell lines confirmed that TSPAN8 was exclusively expressed by invasive, but not non-invasive melanoma cells or normal melanocytes. Immunohistochemistry revealed that TSPAN8 was expressed by melanoma cells in primary melanomas and metastases, but not epidermal cells in healthy skin. The functional role of TSPAN8 was demonstrated by silencing endogenous TSPAN8 with siRNA, reducing invasive outgrowth from tumour spheroids within matrigel without affecting cell proliferation or survival. TSPAN8 expression may enable melanoma cells to cross the cutaneous basement membrane, leading to dermal invasion and progression to metastasis. TSPAN8 could be a promising target in early detection and treatment of melanoma.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6605994