Hahn T, Or R, Segall H, Karov Y
Pediatric Research Laboratory, Kaplan Medical Center, Rehovot, Israel.
Int J Cancer. 1998 Nov 23;78(5):624-8. doi: 10.1002/(sici)1097-0215(19981123)78:5<624::aid-ijc16>3.0.co;2-g.
In patients with neuroblastoma (NB) or breast carcinoma (BC), metastatic disease in the bone marrow (BM) is observed more frequently than at any other site, and a high incidence of BM metastases in these patients is associated with advanced disease and poor prognosis. These observations suggest the presence of BM micro-environmental elements that are favorable for NB and BC tumor cell growth. The influence of normal human BM cell-derived conditioned medium (CM) on clonogenic growth of BC and NB cell lines was investigated in vitro. The effects obtained were compared with those on tumor cells with a lower potential for BM metastasis. CM from unstimulated cultures of normal, healthy, low-density BM cells reproducibly and markedly augmented clonogenic growth of 3 BC and 3 NB cell lines. In contrast, growth of cell lines established from human tumors with differing metastatic propensity was unaffected by BM CM. Initial characterization, using crude BM CM, indicated that mitogenic activity (i) is mediated by peptides released by the non-adherent fraction of low-density BM cells and (ii) is not abolished by neutralizing antibodies against various cytokines known to be produced by BM cells and to regulate hematopoietic cell growth. Our observations suggest that certain specific peptides in the BM micro-environment may be responsible for the preferential growth of NB and BC metastases in BM.
在神经母细胞瘤（NB）或乳腺癌（BC）患者中，骨髓（BM）转移疾病的观察频率高于其他任何部位，并且这些患者中骨髓转移的高发生率与疾病进展和预后不良相关。这些观察结果表明存在有利于NB和BC肿瘤细胞生长的骨髓微环境因素。体外研究了正常人骨髓细胞来源的条件培养基（CM）对BC和NB细胞系克隆生长的影响。将获得的结果与对骨髓转移潜力较低的肿瘤细胞的影响进行比较。来自正常、健康、低密度骨髓细胞未刺激培养物的CM可重复性地显著增强3种BC和3种NB细胞系的克隆生长。相比之下，从具有不同转移倾向的人类肿瘤建立的细胞系的生长不受骨髓CM的影响。使用粗制骨髓CM进行的初步表征表明，促有丝分裂活性（i）由低密度骨髓细胞非贴壁部分释放的肽介导，（ii）不会被针对已知由骨髓细胞产生并调节造血细胞生长的各种细胞因子的中和抗体消除。我们的观察结果表明，骨髓微环境中的某些特定肽可能是NB和BC在骨髓中优先转移生长的原因。
