神經膠質瘤(glioma)是異常增生之膠質細胞（glial cells）所產生的常見腦部原發性腫瘤（primary brain tumor）。大量小膠質細胞(microglia)與巨噬細胞（macrophage）的侵入是神經膠質瘤的特徵。相關研究證實，神經膠質瘤四周所分泌之趨化因子可能在引發小膠質細胞的活化中扮演重要角色，調節腫瘤生成。我們利用動物腦瘤模式，於大腦皮層植入C6神經膠質瘤細胞株後發現，手術後1周Iba1+ 與 ED1+小膠質細胞已滲入腫塊中心。然而在手術後2周腫塊中心部份主要為Iba1+小膠質細胞。另外，手術後第3天，腫塊四周之Iba1+ 與 ED1+小膠質細胞中可發現monocyte chemoattractant protein-1 (MCP-1) 與macrophage inflammatory protein-1 alpha(MIP-1alpha) 表現。文獻得知C6神經膠質瘤能分泌brain-derived neurotrophic factor （BDNF）；但是以BDNF蛋白分子處理小膠質細胞對其MIP-1alpha mRNA表現不受影響。然而利用BDNF處理神經細胞後之培養基（B-NCM）則可提高小膠質細胞中MIP-1alpha mRNA表現量。因BDNF可誘導神經細胞fractalkine mRNA表現量上升，利用fractalkine抗體中和B-NCM後，結果發現fractalkine抗體阻斷B-NCM對小膠質細胞MIP-1alpha mRNA表現量的增加作用。這些研究顯示，B-NCM中的fractalkine無法提高小膠質細胞MIP-1alpha mRNA產量，反而可能影響B-NCM內其他因子所誘導小膠質細胞MIP-1alpha mRNA表現量上升的作用。綜合我們動物與離體實驗顯示，我們推測C6植入後可以藉由引發神經細胞媒介物質產生後，進而誘導神經膠質瘤四周小膠質細胞MIP-1alpha mRNA表現，並促使小膠質細胞的聚集到腫瘤外圍及中心部份。

　　Glioma is the common primary brain tumor derived from the abnormal proliferation of the glia. The infiltration of microglia, brain macrophages, is a characteristic feature of glioma. Several studies have addressed that chemotactic factors secreted around glioma may have the regulatory role in the induction of microglial activation, which is to modulate gliomal formation. We used an animal brain tumor model by injecting C6 glioma cells into the rat cerebral cortex, and found that Iba1+ and ED1+ microglia were infiltrated in the tumor center at 1 week after injection (AI). However, Iba1+ cells were the major microglial population observed in the tumor center at 2 week AI. The expression of monocyte chemoattractant protein-1(MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) were also observed in Iba1+ or ED1+ microglia situated at the periphery of rat brain tumor at 3 day AI. Treatment of microglia with brain-derived neurotrophic factor (BDNF), that has been known to be produced by C6 cells, had no effect on MIP-1alpha mRNA expression. However, the conditioned medium collected from neurons treated with BDNF (B-NCM) can upregulate microglial MIP-1alpha mRNA expression. Since BDNF was shown to increase the expression of neuronal fractalkine mRNA, we investigated the regulatory role of fractalkine in B-NCM using anti-fractalkine antibodies to neutralize the molecule in B-NCM. We found that the blockade of anti-fractalkine antibodies increased MIP-1alpha mRNA in microglia treated with B-NCM. The data demonstrate that fractalkine was not involved in the upregulation of microglial MIP-1alpha mRNA by B-NCM. In contrast, this molecule may contribute to suppress the increase of B-NCM-induced microglial MIP-1alpha mRNA expression. Together, based on our in vivo and in vitro results, we suggest that injected C6 cells may secrete BDNF to induce the production of neuronal factors, which upregulate the expression of MIP-1alpha mRNA in microglia around glioma tumor.

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