Jacob K, Wach F, Holzapfel U, Hein R, Lengyel E, Buettner R, Bosserhoff A K
Department of Dermatology, University of Regensburg Medical School, Germany.
Melanoma Res. 1998 Jun;8(3):211-9. doi: 10.1097/00008390-199806000-00003.
Invasive growth and formation of metastases involve complex interactions between tumour cells, host cells and components of the extracellular matrix. Retinoids, a group of vitamin A derivatives, modulate cell growth and differentiation and have been found to suppress tumour cell invasion in vitro and formation of metastases in vivo. The aim of our study was to investigate changes in proliferation and invasion through membrane barriers in vitro of seven human melanoma cell lines, established from human primary melanomas or metastases, in response to treatment with retinoic acid (RA). These changes were compared with the expression regulation of molecules that have been identified as targets of RA-mediated signal pathways. Invasiveness in vitro was correlated with the origin of the cell lines and was significantly higher in the lines derived from metastases. In all the cell lines proliferation and chemotaxis were inhibited by 10(-5) M RA, but the cell lines established from metastases were significantly more sensitive with respect to inhibition of invasion by RA. The specific expression patterns of MMP-1 and TIMP-2 were detected and regulated by RA in almost all cell lines, whereas expression of MMP-2 and TIMP-1 was not influenced by RA treatment. The most striking difference between the cell lines was a strong downregulation of transforming growth factor-beta (TGF-beta) expression in cell lines derived from metastases when treated with RA in contrast to cell lines from primary melanomas. These data provide evidence that RA modulates growth, chemotaxis and invasion in a broad panel of melanoma cell lines derived both from primary non-metastasized melanomas and metastases. However, distinct molecular mechanisms are involved in mediating these effects.
侵袭性生长和转移的形成涉及肿瘤细胞、宿主细胞和细胞外基质成分之间的复杂相互作用。类视黄醇是一组维生素A衍生物，可调节细胞生长和分化，并且已发现在体外可抑制肿瘤细胞侵袭，在体内可抑制转移的形成。我们研究的目的是调查源自人原发性黑色素瘤或转移灶的7种人黑色素瘤细胞系在体外对维甲酸（RA）治疗的反应中，通过膜屏障的增殖和侵袭变化。将这些变化与已被确定为RA介导信号通路靶点的分子的表达调控进行比较。体外侵袭性与细胞系的起源相关，并且在源自转移灶的细胞系中显著更高。在所有细胞系中，10^(-5)M的RA抑制增殖和趋化性，但源自转移灶的细胞系对RA抑制侵袭的敏感性显著更高。在几乎所有细胞系中，RA检测并调节MMP-1和TIMP-2的特异性表达模式，而MMP-2和TIMP-1的表达不受RA治疗的影响。细胞系之间最显著的差异是，与源自原发性黑色素瘤的细胞系相比，源自转移灶的细胞系在用RA处理时，转化生长因子-β（TGF-β）表达强烈下调。这些数据提供了证据，表明RA可调节源自原发性未转移黑色素瘤和转移灶的多种黑色素瘤细胞系的生长、趋化性和侵袭。然而，介导这些效应涉及不同的分子机制。
