Taraboletti G, Borsotti P, Chirivi R G, Vergani V, Falanga A, Barbui T, Giavazzi R, Rambaldi A
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Int J Cancer. 1997 Jan 6;70(1):72-7. doi: 10.1002/(sici)1097-0215(19970106)70:1<72::aid-ijc11>3.0.co;2-f.
All trans-retinoic acid (ATRA) induces complete remission in acute-promyelocytic-leukemia (APL) patients. This study investigated the adhesive properties of APL cells for the endothelium and the extracellular matrix, their motility and the effect of ATRA on these functions. Blasts from 7 APL patients adhered to resting and IL-1-activated endothelium, to the same degree as normal PMN. Adhesion was partially mediated by ICAM-1 and, for IL-1-activated endothelium, by VCAM-1 and E-selectin. These cells showed less adhesiveness for the matrix than PMN, although they maintained the same substrate preference: they adhered to fibronectin and thrombospondin, but not to laminin and type-IV collagen. Exposure to ATRA in vitro (1 microM for 48 to 96 hr) increased the adhesiveness of APL cells; this effect was particularly evident in the case of sub-endothelial matrix and fibronectin. A similar increment in adhesiveness was observed when comparing cells from 2 patients before and after treatment with ATRA. APL cells migrated in response to fMLP and motility was increased by ATRA. In conclusion, APL cells were less adhesive to the matrix than PMN, but treatment with ATRA considerably enhanced their adhesive properties. This could be important in determining the efflux of leukemic cells from the bone marrow and their tissue infiltration during ATRA therapy.
全反式维甲酸（ATRA）可使急性早幼粒细胞白血病（APL）患者完全缓解。本研究调查了APL细胞与内皮细胞及细胞外基质的黏附特性、它们的迁移能力以及ATRA对这些功能的影响。7例APL患者的原始细胞与静息及白细胞介素-1（IL-1）激活的内皮细胞的黏附程度与正常中性粒细胞相同。黏附部分由细胞间黏附分子-1（ICAM-1）介导，对于IL-1激活的内皮细胞，还由血管细胞黏附分子-1（VCAM-1）和E-选择素介导。这些细胞对基质的黏附性低于中性粒细胞，尽管它们保持相同的底物偏好：它们黏附于纤连蛋白和血小板反应蛋白，但不黏附于层粘连蛋白和IV型胶原。体外暴露于ATRA（1微摩尔/升，48至96小时）可增加APL细胞的黏附性；这种效应在皮下基质和纤连蛋白的情况下尤为明显。比较2例患者治疗前后的细胞时，观察到黏附性有类似增加。APL细胞对N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）有迁移反应，且ATRA可增加其迁移能力。总之，APL细胞对基质的黏附性低于中性粒细胞，但ATRA治疗可显著增强其黏附特性。这在确定ATRA治疗期间白血病细胞从骨髓的流出及其组织浸润方面可能很重要。
