Cross-talk between Schwann cells and neuroblasts influences the biology of neuroblastoma xenografts
Cross-talk between Schwann cells and neuroblasts influences the biology of neuroblastoma xenografts
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DOI：
10.1016/s0002-9440(10)62309-7
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发表时间：
2005-03-01
影响因子：
6
通讯作者：
Cohn, SL
中科院分区：
文献类型：
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作者：
Liu, SQ;Tian, YF;Cohn, SL
神经母细胞瘤（NB）肿瘤具有丰富的神经鞘间质，具有分化的表型，低血管，并与良好的预后相关。这些观察结果表明，雪旺细胞和神经母细胞之间存在串扰；可能影响肿瘤生物学。为了验证这一假设，我们建立了一种浸润小鼠雪旺细胞的新型NB异种移植模型。将人SMS-KCNR NB细胞注入神经束内（坐骨神经植入NB， n = 19）或坐骨神经外（对照组，n = 12）。肿瘤细胞接种后4至12周采集异种移植物进行组织学研究。用S-100和种特异性p75（NGFR）、主要组织相容性复合体和人白细胞抗原抗体对雪旺细胞进行免疫染色。与对照组比较坐骨神经移植NB肿瘤中增殖细胞、浸润雪旺细胞、凋亡细胞、分化成神经细胞和血管的数量。坐骨神经移植物中雪旺细胞的数量明显多于对照组（P < 0.001）。浸润的雪旺细胞s -100阳性，与抗小鼠主要组织相容性复合体Ib和p75（NGFR）反应，但与抗人p75（NGFR）和人白细胞抗原I类抗体不反应。与对照组相比，坐骨神经移植肿瘤中增殖性神经母细胞数量减少，分化性神经母细胞和凋亡细胞数量增加，血管密度降低。我们的研究结果表明，小鼠源性浸润雪旺细胞在体内能够促进人神经母细胞分化，诱导细胞凋亡，抑制细胞增殖和血管生成。
Neuroblastoma (NB) tumors with abundant schwannian stroma have a differentiated phenotype, low vascularity, and are associated with a favorable prognosis. These observations suggest that cross-talk between Schwann cells and neuroblasts; may influence tumor biology. To test this hypothesis, we developed a novel NB xenograft model with infiltrating mouse Schwann cells. Human SMS-KCNR NB cells were injected intrafascicularly (sciatic nerve-engrafted NB, n = 19) or outside the sciatic nerve (control, n = 12). Xenografts were harvested 4 to 12 weeks after tumor cell inoculation for histological studies. Schwann cells were immunostained with S-100 and species-specific p75(NGFR), major histocompatibility complex, and human leukocyte antigen antibodies. The number of proliferating cells, infiltrating Schwann cells, apoptotic cells, differentiated neuroblasts, and blood vessels in the sciatic nerve-engrafted NB tumors were compared to controls. Significantly more Schwann cells were detected in the sciatic nerve-engrafted NB xenografts than controls (P < 0.001). The infiltrating Schwann cells were S-100-positive and reacted with anti-mouse major histocompatibility complex class Ib and p75(NGFR) but not anti-human p75(NGFR) and human leukocyte antigen class I antibodies. The sciatic nerve-engrafted tumors also had lower numbers of proliferating neuroblasts, higher numbers of differentiated neuroblasts and apoptotic cells, and decreased vascular density compared to controls. our results indicate that infiltrating Schwann cells of mouse origin are capable of promoting human neuroblast differentiation, inducing apoptosis, and inhibiting proliferation and angiogenesis in vivo.