Gene expression profiles of human melanoma cells with different invasive potential reveal TSPAN8 as a novel mediator of invasion.
Gene expression profiles of human melanoma cells with different invasive potential reveal TSPAN8 as a novel mediator of invasion.
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具有不同侵袭潜力的人类黑色素瘤细胞的基因表达谱揭示了 TSPAN8 作为一种新型的侵袭介质。
DOI：
10.1038/sj.bjc.6605994
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发表时间：
2011-01-04
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
转移性黑色素瘤需要早期发现，具有治疗耐药性。然而，黑色素瘤转移的最早事件，特别是真皮侵袭，仍然不明确。用寡核苷酸芯片比较了从同一人类黑色素瘤细胞系中选择的两个克隆亚群的基因表达谱，但在皮肤重建中穿越真皮-表皮交界处的能力不同。在26496个cDNA探针中，461个存在差异表达（>2倍；P< 0.001），只有71个基因在侵袭细胞中表达上调。其中，RT-PCR、流式细胞术和western blot分析显示，侵袭性克隆的黑色素瘤细胞中，尚未在黑色素瘤中发现的四联蛋白TSPAN8的mRNA和蛋白水平均上调。有趣的是，TSPAN8是唯一过表达与侵袭性表型相关的四种蛋白。流式细胞术证实，TSPAN8仅在侵袭性黑色素瘤细胞或正常黑色素细胞中表达，而非侵袭性黑色素瘤细胞或正常黑色素细胞中不表达。免疫组织化学表明，TSPAN8在原发性黑色素瘤和转移瘤的黑色素瘤细胞中表达，而在健康皮肤的表皮细胞中不表达。通过用siRNA沉默内源性TSPAN8，证明了TSPAN8的功能作用，减少基质内肿瘤球体的侵袭性生长，而不影响细胞增殖或存活。TSPAN8的表达可能使黑色素瘤细胞穿过皮肤基底膜，导致真皮侵袭并进展到转移。TSPAN8可能是黑色素瘤早期检测和治疗的一个有希望的靶点。
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.
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影响因子：
4.4
作者：
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64.8
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