Hahn T, Or R, Bruchelt G, Malach L, Karov Y, Lefshitz-Mercer B, Evron R, Barak Y
Pediatric Research Institute, Kaplan Hospital, Rehovot, Israel.
Cancer. 1996 Jun 15;77(12):2614-21. doi: 10.1002/(SICI)1097-0142(19960615)77:12<2614::AID-CNCR27>3.0.CO;2-U.
Neuroblastoma (NB) is one of the few tumors known to undergo spontaneous regression. Its progression, however, often leads to bone marrow (BM) metastasis. Proliferation and differentiation of human NB cells may be regulated in vitro by a variety of biologic agents, some of which are released by low-density BM and peripheral blood (PB) cells. Little is known regarding BM cell-derived control of NB cell growth and differentiation.
The proliferative and differentiative responses of NB cells, to BM cell-, and to PB cell-derived conditioned medium (CM) were evaluated in comparison to cytokine-induced responses.
CM from unstimulated cultures of low density BM and PB cells, from healthy donors, from newborn infants, and from NB patients, significantly and reproducibly stimulate NB cell growth in vitro. The intensity of CM-induced stimulation was not attained by recombinant human tumor necrosis factor (rhTNF), interferon (rhIFN), or granulocyte-monocyte colony stimulating factor (rhGM-CSF); and although epidermal growth factor (rhEGF) and transforming growth factor alpha (rhTGF alpha) were strongly stimulatory, neutralizing antibodies against each of these agents did not affect CM-derived activity. In contrast to growth stimulation, differentiation of CM-treated NB cells, was reproducibly suppressed, as reflected in abrogation of neuronal cell morphology as well as of neurofilament and neuron specific enolase expression.
Spontaneous regression of NB tumors, on one hand and BM metastasis on the other may be associated with the extent and nature of the NB cell response to regulatory activity released by BM and PB cells.
神经母细胞瘤（NB）是已知的少数可发生自发消退的肿瘤之一。然而，其进展往往会导致骨髓（BM）转移。人NB细胞的增殖和分化在体外可能受到多种生物因子的调节，其中一些由低密度BM细胞和外周血（PB）细胞释放。关于BM细胞对NB细胞生长和分化的控制知之甚少。
与细胞因子诱导的反应相比，评估NB细胞对BM细胞和PB细胞来源的条件培养基（CM）的增殖和分化反应。
来自健康供体、新生儿和NB患者的低密度BM和PB细胞未刺激培养物的CM，在体外能显著且可重复地刺激NB细胞生长。重组人肿瘤坏死因子（rhTNF）、干扰素（rhIFN）或粒细胞-单核细胞集落刺激因子（rhGM-CSF）未达到CM诱导刺激的强度；尽管表皮生长因子（rhEGF）和转化生长因子α（rhTGFα）具有强烈的刺激作用，但针对这些因子的中和抗体并不影响CM的活性。与生长刺激相反，CM处理的NB细胞的分化可重复受到抑制，这表现为神经元细胞形态以及神经丝和神经元特异性烯醇化酶表达的消失。
一方面，NB肿瘤的自发消退，另一方面，BM转移可能与NB细胞对BM和PB细胞释放的调节活性的反应程度和性质有关。
