研究放射線照射後的腦組織對於腦瘤生長的影響

Brain Tumor Bed Effect

林琦珉

指導教授 ： 江啟勳

國立清華大學/原子科學院/生醫工程與環境科學系/碩士(2011年)

https://doi.org/10.6843/NTHU.2011.00278

摘要

放射線治療幾乎為所有腦腫瘤的主要治療方式之一，但臨床上在放射線治療過後腦腫瘤復發的比例也相當高，且往往復發的腦腫瘤治癒率更低。儘管許多研究都將焦點放在如何增加腦腫瘤放射線治療的效果上，復發的腦腫瘤在放射線照射後的微環境變化卻仍然不清楚。我們利用小鼠星狀細胞瘤細胞株，ALTS1C1，生長在放射線預先照射(Pre-IR)的腦組織，模擬一個臨床上腦腫瘤復發的微環境模型，來研
究在放射線照射前後腦腫瘤細胞面對不同微環境變化時的行為反應。我們首先探討放射線照射對於ALTS1C1 腦腫瘤微環境的影響，結果發現腫瘤生長在Pre-IR 後的腦組織中會造成較低的腫瘤血管密度、較多的缺氧和壞死區域以及腫瘤相關巨噬細胞(TAMs)聚集於缺氧區域等被稱為是腫瘤床效應(Tumor Bed Effect; TBE)的情形。然而TBE是否造成腫瘤生長及致死速率的延遲，還受到其它許多像是Pre-IR劑量、基質細胞衍生因子-1(SDF-1)或是組織的種類等因素的調控。例如當我們使用腫瘤血管密度、缺氧或壞死區域作為TBE的指標時，在Pre-IR 劑量為8~15 Gy 時依劑量提升會產生較高程度的TBE，但腫瘤生長延遲的情形只在Pre-IR 劑量為15 Gy 時會發生。然而當ALTS1C1 腫瘤細胞的SDF-1 表現受到siRNA 方式所抑制時，腫瘤在15 Gy 的Pre-IR 環境中生長延遲的情形就會消失。此現象指出復發腦腫瘤的生長速率會受到腫瘤細胞與其微環境之間的交互作用所調控，
進一步釐清這些機制將有助於我們了解在放射線治療後復發的腦腫瘤，並開發更有效的復發腫瘤治療方式。

關鍵字

腦瘤 ； 腫瘤床效應 ； 放射線預先照射 ； 腫瘤微環境 ； 神經膠質瘤

並列摘要

Radiotherapy (RT) is a major strategy for treating brain tumors, but the relative high percentage of recurrent brain tumors after RT is frequently reported clinically and is associated with a lower cure rate. Despite many studies focus on the methods to improve the efficacy of RT for brain tumor, the alteration of the microenvironments in recurrent brain tumor after RT is still not clear. To investigate the behaviors of recurrent brain tumors after RT, we used a murine astrocytoma, ALTS1C1, growing from pre-irradiated (pre-IR) brain tissues as a pre-clinical brain tumor recurrent model. Using this model, we found that tumors grown from pre-IR brain tissues have lower microvascular density (MVD), more hypoxic and necrotic regions, and the aggregation of tumor-associated macrophages (TAMs) in hypoxic regions, which is generally called tumor bed effect (TBE). However, whether TBE would result in tumor growth delay still depends on many other factors, such as pre-IR dose, the expression of stromal-cell-derived factor-1 (SDF-1), or type of tissues. For example, using MVD, hypoxia, or necrosis as the readout for TBE, a good pre-IR dose response could be found between 8 ~ 15 Gy, but tumor growth delay was only found in 15 Gy pre-IR group. When the expression of SDF-1 by ALTS1C1 cells was suppressed by siRNA approach, the tumor growth delay in 15 Gy pre-IR group disappeared. This indicates that the growth rate of recurrent brain tumor is the result of the interplay between tumor cells and irradiated tumor microenvironments. To understand the mechanisms behind them will

並列關鍵字

ALTS1C1 ； TBE ； pre-irradiation ； microenvironment ； glioma

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