M2巨噬細胞對小鼠乳腺癌細胞生長之影響

The role of M2 macrophage in modulation of breast cancer growth

陳建名(Chien-Ming Chen)

指導教授 ： 李宏謨

共同指導教授 ： 戴明燊(Ming-Shen Dai)

臺北醫學大學/醫學科技學院/醫學檢驗暨生物技術學系所/碩士(2016年)

摘要

背景與目的：減緩甚至消除腫瘤生長和轉移一直是癌症治療的主要目標。腫瘤相關巨噬細胞（tumor-associated macrophages, TAM）的浸潤（infiltration）所誘發之發炎反應會促進腫瘤的生長和存活（proliferation and survival）並誘發腫瘤血管新生與轉移（angiogenesis and metastasis），其中巨噬細胞分泌的抗酒石酸性磷酸酶（tartrate-resistant acid phosphatase, TRAcP）可能扮演重要角色。因此本研究欲探討M2巨噬細胞是否經由調控抗酒石酸性磷酸酶的表現促進腫瘤生長速度，以及其相關機制。
方法：我們將M2巨噬細胞與JC乳腺癌細胞經由不同組合方式(單純注射JC、M2和JC一起注射，先注射M2 30分鐘後再注射JC)注射至小鼠的乳腺皮下，經過14天後測量其腫瘤生長的速度、大小和重量、腫瘤的抗酒石酸性磷酸酶表現和血清中抗酒石酸性磷酸酶5a的濃度。
結果：實驗結果發現預先注射M2巨噬細胞30分鐘後再注射JC乳腺癌細胞之組別與其他兩組（單純注射JC以及M2和JC一起注射）比較能顯著促進小鼠乳腺癌細胞之生長，而且這與腫瘤抗酒石酸性磷酸酶的表現增加有關。
結論：M2巨噬細胞可以藉由調節抗酒石酸性磷酸酶影響腫瘤相關環境，進而顯著促進小鼠乳腺癌細胞之生長。因此，抗酒石酸性磷酸酶可能可作為臨床監測乳癌癌症預後的生物指標或標靶治療的目標。

關鍵字

腫瘤相關巨噬細胞 ； 白血球浸潤 ； 抗酒石酸性磷酸酶環境 ； 微環境 ； 癌症相關發炎反應 ； 先天性免疫反應 ； 後天性免疫反應 ； 細胞激素 ； 化學激素 ； 巨噬細胞

並列摘要

Background and purpose:
Alleviating or even eliminating tumor growth and metastasis has been the main goal of cancer treatment. Tumor-associated macrophages (TAM, also called M2 macrophage) infiltration-induced inflammatory responses not only promote tumor growth and survival, but trigger tumor angiogenesis and metastasis. The tartrate-resistant acid phosphatase (TRAcP) secreted by macrophages may play an important role. This study aimed to investigate whether M2 macrophages promoted the growth of tumor by regulating the expression of TRAcP and its mechanisms.

Method:
M2 macrophages and JC breast cancer cells were injected into the mammary glands of BALB/c mice via different combinations: 1) JC alone; 2) M2 and JC at the same time; 3) M2 was injected 30 min before the injection of JC. After 14 days, the rate and size of tumor growth, the body weight of the mice, the expression of TRAcP in tumors, and the level of TRAcP in serum were measured to compare the baseline data of above parameters.

Statistic Analysis:
All data showed by MEAN±SD, using Two-Way Repeated Measures ANOVA to compared different groups and different times for the body weight and subcutaneous tumor size of the mice. One the other hand, using One-Way ANOVA to compared different groups for tumor size of the mice. Statistical software is SPSS.

Result:
The results showed that the injection of M2 macrophages 30 min before the injection of JC significantly promoted tumor growth relative to other two groups (JC only or M2 and JC were injected at the same time), and this was associated with the expression of TRAcP in tumors and serum.

Conclusion:
M2 macrophages may regulate tumor-related environment by modulating the level of TRAcP in tumors and serum, and thereby have significant impacts on the growth of breast cancer cells in mice. Therefore, TRAcP may be a promising biomarker for clinical prognosis or a target for oncological therapy in mice breast cancer.

並列關鍵字

tumor-associated macrophages, TAM ； leukocyte infiltration ； tartrate-resistant acid phosphatase, TRAcP ； niche ； microenvironment ； cancer-related inflammation ； innate immunity ； acquired immunity ； cytokines ； chemokines ； macrophage

參考文獻

Reference

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