Kuphal Silke, Bauer Richard, Bosserhoff Anja-Katrin
Institute of Pathology, University of Regensburg, Germany.
Cancer Metastasis Rev. 2005 Jun;24(2):195-222. doi: 10.1007/s10555-005-1572-1.
Cell adhesion and migration are essential for embryonic development, tissue regeneration, but also for tumor development. The physical link between the extracellular matrix (ECM) and the actin cytoskeleton is mainly mediated by receptors of the integrin family. Through signals transduced upon integrin ligation to ECM proteins, this family of proteins plays key roles in regulating tumor growth and metastasis as well as tumor angiogenesis. During melanoma development, changes in integrin expression, intracellular control of integrin functions and signals perceived from integrin ligand binding impact upon the ability of tumor cells to interact with their environment and enable melanoma cells to convert from a sessile, stationary to a migratory and invasive phenotype. Antagonists of several integrins are now under evaluation in clinical trials to determine their potential as therapeutics for malignant melanoma and other kinds of cancer.
细胞黏附和迁移对于胚胎发育、组织再生以及肿瘤发展都至关重要。细胞外基质(ECM)与肌动蛋白细胞骨架之间的物理连接主要由整合素家族的受体介导。通过整合素与ECM蛋白连接时转导的信号,这类蛋白在调节肿瘤生长、转移以及肿瘤血管生成中发挥关键作用。在黑色素瘤发展过程中,整合素表达的变化、整合素功能的细胞内调控以及整合素配体结合所感知的信号,都会影响肿瘤细胞与周围环境相互作用的能力,使黑色素瘤细胞从固着、静止的表型转变为迁移和侵袭性表型。目前,几种整合素拮抗剂正在临床试验中进行评估,以确定它们作为恶性黑色素瘤和其他癌症治疗药物的潜力。