PDF(Pubmed)
Abstract：
BACKGROUND: The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma.
METHODS: A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization.
RESULTS: Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout.
CONCLUSIONS: Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF.
METHODS: A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization.
RESULTS: Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout.
CONCLUSIONS: Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF.
摘要：
背景：肿瘤炎症微环境在癌症进展中的作用，尤其是前列腺癌，被广泛认可。ELL相关因子2（EAF2），一种已经在前列腺中发现的肿瘤抑制剂，在前列腺癌中经常下调。早期的研究表明，EAF2基因敲除的小鼠表现出炎性细胞大量浸润到前列腺基质中。
方法：选择了一个队列，该队列包括38例诊断为前列腺癌并随后接受根治性前列腺切除术（RP）的患者。这些患者根据Gleason评分系统进行病理分级，并分为两组。该选择的目的是使用免疫组织化学(IHC)染色来研究EAF2和CD163之间的潜在相关性。此外,进行了体外实验以验证EAF2表达之间的关系，巨噬细胞迁移和极化。
结果：我们的研究表明，在人类前列腺癌标本中，EAF2的表达明显下调，这种减少与浸润癌组织的CD163阳性巨噬细胞的数量呈负相关。细胞共培养实验表明，当敲除EAF2时，肿瘤细胞对巨噬细胞的趋化作用增强，巨噬细胞分化成肿瘤相关巨噬细胞（TAM）。此外,应用细胞因子蛋白芯片显示EAF2敲除后趋化因子巨噬细胞移动抑制因子(MIF)的表达增加。
结论：我们的发现提示EAF2通过MIF参与前列腺癌中CD163阳性巨噬细胞的浸润。
方法：选择了一个队列，该队列包括38例诊断为前列腺癌并随后接受根治性前列腺切除术（RP）的患者。这些患者根据Gleason评分系统进行病理分级，并分为两组。该选择的目的是使用免疫组织化学(IHC)染色来研究EAF2和CD163之间的潜在相关性。此外,进行了体外实验以验证EAF2表达之间的关系，巨噬细胞迁移和极化。
结果：我们的研究表明，在人类前列腺癌标本中，EAF2的表达明显下调，这种减少与浸润癌组织的CD163阳性巨噬细胞的数量呈负相关。细胞共培养实验表明，当敲除EAF2时，肿瘤细胞对巨噬细胞的趋化作用增强，巨噬细胞分化成肿瘤相关巨噬细胞（TAM）。此外,应用细胞因子蛋白芯片显示EAF2敲除后趋化因子巨噬细胞移动抑制因子(MIF)的表达增加。
结论：我们的发现提示EAF2通过MIF参与前列腺癌中CD163阳性巨噬细胞的浸润。
