探討 HNMT 在神經膠質瘤生長中所扮演的角色
神經膠質瘤源於神經膠細胞，其數量占大腦細胞的百分之九十，功能 為分泌神經成長因子誘發神經纖維生長、形成髓鞘及血腦屏障。最常 見的神經膠質瘤為神經膠母細胞瘤，神經膠質瘤形成的因素至今尚未 完全明朗。由於神經膠質瘤生長邊界不明確，以手術方式無法清除乾 淨，對於化學治療及放射線治療具有高度的抵抗性而不易治療。另一 方面，因為神經膠質瘤的高度入侵性及致死率，使得科學家們致力於 去開發及尋找新的治療方法及治療標的基因。之前研究發現同時給予 i nterlukin-2 (IL-2) 及組織胺治療能有效地抑制惡性神經膠質瘤的生長及 血管新生，這也暗示著組織胺有抑制神經膠質瘤生長的功能。組織胺 在細胞內主要藉由 histamine-N-methyltransferase (HNMT) 來代謝。前 人的實驗結果已經證實組織胺含量及其代謝物和癌症有著一定的相關 性，然而卻沒有相關的文獻直接指出 HNMT 和神經膠質瘤的關係或探 討 HNMT 相關的致病機轉，本論文發現不論是神經膠質瘤組織或細胞 株， HNMT 的表現量都較正常腦組織多，高度表現的 HNMT 暗示著 抗癌的組織胺含量下降。另一方面，神經膠質瘤促進因子之一的 epith elial growth factor (EGF) 會增加 HNMT 的表現及 HNMT 在細胞中位置 的轉移。針對致命的神經膠質瘤，我們的結果提供 HNMT 是另一個新 的治療標的。
Study of histamine-N-methyltransferase (HNMT) in the glioma
Giloma derive from glial cell, which contribute about 90% of brain cells. The funct ions of glial cells are offering support and nutrition, forming myelin sheath and blo od brain barrier.The most common glioma is glioblastoma multiforme (GBM) and t he possible causes are not fully understood. Neurosurgery unable to remove the gli oma from normal brain clearly ； Glioma even resisten to high dose of radiotherap y and chemotherapy. The prognosis of malignant glioma remains dismal and the est imated median survival time is <1 year.It is emergent to develop new therapic polic y and find out target genes. Previous data investigate that cotreatment with interleu kin-2 (IL-2) and histamine inhibits growth and angiogenesis in malignant glioma. It also suggests that histamine has function of tumor suppression. In cytosol, histamin e is metabolized by histamine-N- methyltransferase (HNMT). The concentration of histamine and its products have association with glioma. However, there is no direc t evidence to investigate the roles of HNMT in growth and pathogenesis of glioma.
Our data demonstrate that either specisement of GBM or glioma cell lines express more HNMT than normal brain tissue. More amount of HNMT suggests less tumor spressive histamine. On the other hands, we also find that epidermal growth factor (EGF), a glioma inducing factor, increases the expression of HNMT and changes th e location of HNMT in glioma cell line. Collectively, our data provide hint that HN MT is another noval theraptic target for deadly glioma.
