Maltseva D V, Rodin S A
Scientific Research Center BioKlinikum, Moscow, 115088 Russia.
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE17177 Sweden.
Mol Biol (Mosk). 2018 May-Jun;52(3):411-434. doi: 10.7868/S0026898418030059.
Laminins are a family of extracellular heterotrimeric glycoproteins that are the main structural component of basement membranes (BMs), perform a barrier function, and are important for adhesion, differentiation, migration, and resistance to apoptosis of various cells, including cancer cells. The review summarizes the current knowledge of how laminins produced by cancer and normal cells influence the key stages of carcinogenesis. Laminin 332 (LN-332) and LN-111 enhance proliferation of certain cancer cells and increase the tumour growth. LN-111 increases resistance to apoptosis, induces differentiation, and inhibits the epithelial-mesenchymal transition (EMT) of cancer cells. LN-332 is associated with higher adhesion and higher migration potential of cancer cells. LN-411 and LN-421 significantly increase motility of cancer cells. LN-332 and LN-511 facilitate cell-cell adhesion and affect the efficacy of cell-cell interactions. The laminin chains α4 and α5 are important for the development and function of blood and lymphatic vessels. The expression ratio of the α4 and α5 laminin chains defines the BM permeability to leukocytes and, presumably, cancer cells in blood and lymphatic vessels. Interactions between LN-511 and α2-containing laminins enhance self-renewal and survival of circulating cancer stem cells. Moreover, laminins are involved in the formation of premetastatic niches and new colonies. Endogenous expression of the α4 laminin chain stimulates proliferation of individualised circulating cancer cells in vitro and in vivo and facilitates micrometastasis.
层粘连蛋白是一类细胞外异源三聚体糖蛋白,是基底膜(BM)的主要结构成分,具有屏障功能,对包括癌细胞在内的各种细胞的黏附、分化、迁移和抗凋亡至关重要。本文综述了目前关于癌细胞和正常细胞产生的层粘连蛋白如何影响致癌关键阶段的知识。层粘连蛋白332(LN-332)和LN-111可增强某些癌细胞的增殖并促进肿瘤生长。LN-111可增加细胞对凋亡的抗性,诱导分化,并抑制癌细胞的上皮-间质转化(EMT)。LN-332与癌细胞的更高黏附性和更高迁移潜能相关。LN-411和LN-421可显著增加癌细胞的运动性。LN-332和LN-511促进细胞间黏附并影响细胞间相互作用的效果。层粘连蛋白链α4和α5对血管和淋巴管的发育及功能很重要。α4和α5层粘连蛋白链的表达比例决定了基底膜对白细胞以及可能对血管和淋巴管中癌细胞的通透性。LN-511与含α2层粘连蛋白之间的相互作用可增强循环癌干细胞的自我更新和存活能力。此外,层粘连蛋白参与了前转移微环境和新菌落的形成。α4层粘连蛋白链的内源性表达在体外和体内均可刺激个体化循环癌细胞的增殖,并促进微转移。