Vacca A, Frigeri A, Ribatti D, Nicchia G P, Nico B, Ria R, Svelto M, Dammacco F
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University School, Bari, Italy.
Br J Haematol. 2001 May;113(2):415-21. doi: 10.1046/j.1365-2141.2001.02738.x.
The erythrocyte water channel aquaporin 1 (AQP1) is expressed in multiple absorptive and secretory epithelia including the capillary endothelia. Immunoblot analysis showed that bone marrow biopsies of patients with active multiple myeloma (MM) display significantly higher levels of AQP1 than those from patients with non-active MM, whose values are higher, but to a lesser extent, than those of patients with monoclonal gammopathies of undetermined significance (MGUS). Values of MGUS overlapped those of patients with anaemia as a result of iron or vitamin B12 deficiencies (called 'benign anaemias'). Immunohistochemistry and computerized image analysis of AQP1 highlighted bone marrow microvessels whose area per microscopic field was significantly greater in patients with active MM, and always larger than and closely correlated with the microvessel area when assessed with factor VIII-related antigen/von Willebrand's factor (FVIII-VWF). The intensity of AQP1 expression by microvessels evaluated using image analysis was significantly greater in active than non-active MM and in the latter over MGUS or benign anaemias. It is suggested that, among plasma cell tumours, AQP1 expression is preferentially associated with microvessels of MM and that the highest degree of expression occurs in active MM in step with enhanced angiogenesis, in which AQP1 recognizes more immature neovessels than FVIII-VWF. It may, perhaps, favour angiogenesis in a positive loop and, hence, MM progression, and thus be applied for therapeutic vascular targeting.
红细胞水通道蛋白1（AQP1）在包括毛细血管内皮在内的多种吸收性和分泌性上皮中表达。免疫印迹分析显示，活动性多发性骨髓瘤（MM）患者的骨髓活检显示AQP1水平显著高于非活动性MM患者，而非活动性MM患者的AQP1水平虽高于意义未明的单克隆丙种球蛋白病（MGUS）患者，但升高程度较小。MGUS患者的值与因铁或维生素B12缺乏导致贫血的患者（称为“良性贫血”）的值重叠。对AQP1进行免疫组织化学和计算机图像分析，突出显示了骨髓微血管，在活动性MM患者中，每个显微镜视野的微血管面积显著更大，并且在用VIII因子相关抗原/血管性血友病因子（FVIII-VWF）评估时，其总是大于微血管面积且与微血管面积密切相关。通过图像分析评估，微血管中AQP1的表达强度在活动性MM中显著高于非活动性MM，在非活动性MM中高于MGUS或良性贫血。提示在浆细胞肿瘤中，AQP1表达优先与MM的微血管相关，并且在活动性MM中，随着血管生成增强，AQP1表达程度最高，其中AQP1识别的新生血管比FVIII-VWF识别的新生血管更不成熟。它可能在一个正反馈回路中促进血管生成，从而促进MM进展，因此可用于治疗性血管靶向。
