Vanderkerken K, De Greef C, Asosingh K, Arteta B, De Veerman M, Vande Broek I, Van Riet I, Kobayashi M, Smedsrod B, Van Camp B
Department of Haematology and Immunology, Free University Brussels, Belgium.
Br J Cancer. 2000 Feb;82(4):953-9. doi: 10.1054/bjoc.1999.1024.
One of the main characteristics of multiple myeloma cells is their predominant localization in the bone marrow. It is, however, unclear whether this is due to a selective initial entry, or whether this entry is more random and other processes like survival and/or growth stimulation, only present in the medullar microenvironment, are unique. To investigate this, in vivo homing kinetics of murine 5T2MM cells shortly after injection were assessed in bone marrow, liver, spleen, lungs, heart, intestines, kidney and testis by tracing of radiolabelled cells, by immunostaining of isolated cells and by polymerase chain reaction analysis. We demonstrated the presence of 5T2MM cells in bone marrow, spleen and liver with all other organs being negative. Adhesion assays of 5T2MM cells to different types of endothelial cells demonstrated a selective adhesion of 5T2MM cells to bone marrow and liver and not to lung endothelial cells. We here demonstrate that the specific in vivo localization of the 5T2MM cells is a result of the combination of a selective entry/adhesion of the 5T2MM cells in the bone marrow, spleen and liver, and a selective survival and growth of these tumour cells in the bone marrow and spleen but not in the liver.
多发性骨髓瘤细胞的主要特征之一是它们主要定位于骨髓。然而,目前尚不清楚这是由于选择性的初始进入,还是这种进入更为随机,而诸如存活和/或生长刺激等其他过程(仅存在于骨髓微环境中)才是独特的。为了对此进行研究,通过追踪放射性标记的细胞、对分离出的细胞进行免疫染色以及聚合酶链反应分析,评估了注射后不久小鼠5T2MM细胞在骨髓、肝脏、脾脏、肺、心脏、肠道、肾脏和睾丸中的体内归巢动力学。我们证明了在骨髓、脾脏和肝脏中存在5T2MM细胞,而所有其他器官均为阴性。5T2MM细胞与不同类型内皮细胞的黏附试验表明,5T2MM细胞选择性地黏附于骨髓和肝脏,而不黏附于肺内皮细胞。我们在此证明,5T2MM细胞在体内的特异性定位是5T2MM细胞在骨髓、脾脏和肝脏中选择性进入/黏附以及这些肿瘤细胞在骨髓和脾脏而非肝脏中选择性存活和生长共同作用的结果。