Uong Audrey, Zon Leonard I
Stem Cell Program and Division of Hematology/Oncology, Children's Hospital Boston, Boston, Massachusetts, USA.
J Cell Physiol. 2010 Jan;222(1):38-41. doi: 10.1002/jcp.21935.
Melanocytes are pigment-producing cells in the skin of humans and other vertebrates. A number of genes involved in melanocyte development and vertebrate pigmentation have been characterized, largely through studies of a diversity of pigment mutations in a variety of species. Embryonic development of the melanocyte initiates with cell fate specification in the neural crest, which is then followed by cell migration and niche localization. Many genes involved in melanocyte development have also been implicated in the development of melanoma, an aggressive and fatal form of skin cancer that originates in the melanocyte. Although early stage melanomas that have not spread to the lymph nodes can be excised with little risk of recurrence, patients diagnosed with metastatic melanoma have a high mortality rate due to the resistance of most tumors to radiotherapy and chemotherapy. Transformed melanocytes that develop into melanomas proliferate abnormally and often begin to grow radially in the skin. Vertical growth can then follow this radial growth, leading to an invasion through the basement membrane into the underlying dermis and subsequent metastasis. It is still unclear, however, how a normal melanocyte becomes a melanoma cell, and how melanoma utilizes the properties of the normal melanocyte and its progenitors in its progression. The goal of this mini-review is to highlight the role of melanocyte developmental pathways in melanoma, and to discuss recent studies and tools being used to illuminate this connection.
黑素细胞是人类和其他脊椎动物皮肤中产生色素的细胞。通过对多种物种中各种色素突变的研究,许多参与黑素细胞发育和脊椎动物色素沉着的基因已得到表征。黑素细胞的胚胎发育始于神经嵴中的细胞命运特化,随后是细胞迁移和微环境定位。许多参与黑素细胞发育的基因也与黑色素瘤的发生有关,黑色素瘤是一种起源于黑素细胞的侵袭性致命皮肤癌。虽然尚未扩散到淋巴结的早期黑色素瘤可以切除且复发风险很小,但被诊断为转移性黑色素瘤的患者死亡率很高,因为大多数肿瘤对放疗和化疗具有抗性。发展成黑色素瘤的转化黑素细胞异常增殖,通常开始在皮肤中呈放射状生长。然后这种放射状生长之后会出现垂直生长,导致通过基底膜侵入下面的真皮并随后发生转移。然而,目前仍不清楚正常的黑素细胞如何变成黑色素瘤细胞,以及黑色素瘤在其进展过程中如何利用正常黑素细胞及其祖细胞的特性。本综述的目的是强调黑素细胞发育途径在黑色素瘤中的作用,并讨论用于阐明这种联系的最新研究和工具。