Satyamoorthy K, Herlyn M
Center for Molecular and Cellular Biology, Science Center, Third Floor, MAHE, Manipal 576119, India.
Cancer Biol Ther. 2002 Jan-Feb;1(1):14-7. doi: 10.4161/cbt.1.1.32.
Melanoma develops from a series of architectural and phenotypically distinct stages and becomes progressively aggressive culminating in metastasis. Over the years, considerable progress has been made in understanding the biological, pathological and immunological aspects of human melanoma progression. Epidemiological and experimental studies have suggested that intense exposures during early childhood to UV radiation may lead to melanoma in adults, but molecular and genetic studies have revealed few autosomal abnormalities, infrequent mutational spectra and very little epistatic and epigenetic mechanisms. At the cellular level it has become clear that deregulated homeostatic control in the skin microenvironment occurs through alterations in the expression of specific proteins. These include growth factors and their receptors, adhesion molecules and their ligands, proteases and their substrates, and transcription factors and their target genes. Like in most other human tumors, there are alterations in the regulatory networks involving signal transduction in human melanoma. Appropriate models mimicking the human disease have been developed. However, these have not yet led to major advances in delineating the precise molecular determinants responsible for melanoma progression. Results from recent studies have put more impetus on identification of new molecules that promise to become better therapeutic targets. This review focuses on the most recent progress in understanding the molecular determinants of tumor progression with a particular emphasis on melanoma as a biological responder to altered homeostasis.
黑色素瘤由一系列结构和表型不同的阶段发展而来，并逐渐变得具有侵袭性，最终导致转移。多年来，在理解人类黑色素瘤进展的生物学、病理学和免疫学方面取得了相当大的进展。流行病学和实验研究表明，儿童早期强烈暴露于紫外线辐射可能导致成人患黑色素瘤，但分子和遗传学研究显示常染色体异常很少、突变谱不常见，上位性和表观遗传机制也很少。在细胞水平上，已经清楚的是，皮肤微环境中稳态控制失调是通过特定蛋白质表达的改变而发生的。这些蛋白质包括生长因子及其受体、黏附分子及其配体、蛋白酶及其底物，以及转录因子及其靶基因。与大多数其他人类肿瘤一样，人类黑色素瘤中涉及信号转导的调控网络存在改变。已经开发出模拟人类疾病的合适模型。然而，这些模型尚未在确定导致黑色素瘤进展的精确分子决定因素方面取得重大进展。最近的研究结果更推动了对有望成为更好治疗靶点的新分子的鉴定。本综述重点关注在理解肿瘤进展分子决定因素方面的最新进展，特别强调黑色素瘤作为对改变的稳态的生物学反应者。
