Dvořánková Barbora, Szabo Pavol, Kodet Ondřej, Strnad Hynek, Kolář Michal, Lacina Lukáš, Krejčí Eliška, Naňka Ondřej, Šedo Aleksi, Smetana Karel
Institute of Anatomy, Charles University, 1st Faculty of Medicine, U Nemocnice 3, 128 00, Prague, Czech Republic.
BIOCEV, Průmyslová 595, 252 50, Vestec, Czech Republic.
Protoplasma. 2017 May;254(3):1143-1150. doi: 10.1007/s00709-016-1038-z. Epub 2016 Nov 3.
Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.
全球恶性黑色素瘤的发病率正在上升。虽然肿瘤的初始阶段可以通过简单的手术轻松治疗,但晚期阶段的治疗相当有限。黑色素瘤细胞会在患者体内迅速扩散,形成多个转移灶。因此,生存率很低。所以,黑色素瘤研究的重点在于早期诊断以及开发新的、更有效的治疗方案。恶性黑色素瘤起源于黑素细胞,黑素细胞可保护有丝分裂活跃的角质形成细胞免受紫外线照射造成的损伤。黑素细胞起源于神经嵴,随后迁移至表皮。当将黑色素瘤细胞植入早期胚胎时,黑色素瘤细胞、黑素细胞和神经嵴干细胞之间的关系就会显现出来:它们使用与正常神经嵴细胞相似的迁移途径。此外,在这个实验模型中,这些黑色素瘤细胞的恶性潜能被过度激发,这可能是由于微环境重编程所致。这一观察结果证明了微环境在黑色素瘤生物学中的关键作用。事实上,恶性肿瘤总体上代表着复杂的生态系统,其中多种细胞类型会影响基因发生突变的癌细胞的生长。这一概念直接适用于恶性黑色素瘤。我们的综述文章重点关注可用于治疗目的的、改变黑色素瘤细胞间相互作用的可能策略。