Clinical Significance of Folate Receptor β-expressing Tumor-associated Macrophages in Pancreatic Cancer
Clinical Significance of Folate Receptor β-expressing Tumor-associated Macrophages in Pancreatic Cancer
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DOI：
10.1245/s10434-012-2263-0
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发表时间：
2012-07-01
影响因子：
3.7
通讯作者：
Natsugoe, Shoji
中科院分区：
文献类型：
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作者：
Kurahara, Hiroshi;Takao, Sonshin;Natsugoe, Shoji
为研究胰腺癌患者胰腺肿瘤微环境中表达叶酸受体β（FR β（+））的巨噬细胞的出现和分布及其与转移和预后的关系，从76例接受根治性切除术的胰腺癌患者中获得肿瘤样本。这些患者均未接受任何术前化疗或放疗。使用新开发的抗人FR β单克隆抗体和CD68抗体，通过免疫组织化学和免疫荧光染色检查每个肿瘤标本中的FR β（+）和肿瘤浸润（CD68（+））巨噬细胞。观察肿瘤的形态、分布、血管内皮生长因子（VEGF）在表达FR β或CD68（+）的巨噬细胞上的表达以及肿瘤微血管密度（MVD）。采用对数秩检验和考克斯比例风险回归分析研究CD68（+）或FR β（+）巨噬细胞、临床病理因素和总生存率之间的关系。FR β（+）巨噬细胞在肿瘤浸润前沿的血管周围区域突出，并且在CD68（+）巨噬细胞中具有VEGF表达的特定亚群。FR β（+）巨噬细胞是胰腺癌肿瘤相关巨噬细胞中的一个新的亚群，可能通过与肿瘤细胞和血管的相互作用在肿瘤微环境中发挥重要作用，并与胰腺癌的全身转移有关。FR β（+）巨噬细胞有望成为胰腺癌的靶向治疗药物。
To examine the appearance and distribution of folate receptor beta-expressing (FR beta(+)) macrophages in the pancreatic tumor microenvironment and their relationship to metastasis and prognosis in pancreatic cancer patients.Tumor samples were obtained from 76 patients with pancreatic cancer who underwent curative resection. None of these patients had received any preoperative chemotherapy or radiotherapy. Both FR beta(+) and tumor-infiltrating (CD68(+)) macrophages were examined in each tumor specimen by immunohistochemical and immunofluorescence staining using a newly developed anti-human FR beta monoclonal antibody and CD68 antibody. The appearance, distribution, expression of vascular endothelial growth factor (VEGF) on FR beta-expressing or CD68(+) macrophages, and tumor microvessel density (MVD) were assessed. Log rank test and Cox proportional hazard regression were used to investigate the associations among CD68(+) or FR beta(+) macrophages, clinicopathologic factors, and overall survival.FR beta(+) macrophages were prominent in the perivascular regions of the tumor-invasive front and a specific subset with VEGF expression in the CD68(+) macrophages. A high number of FR beta(+) macrophages showed a positive association with high MVD, a high incidence of hematogenous metastasis, and a poor prognosis in pancreatic cancer patients.FR beta(+) macrophages are a novel subset of tumor-associated macrophages in pancreatic cancer and may play an important role in the tumor microenvironment in association with systemic metastasis through the interaction with tumor cells and vessels. FR beta(+) macrophages may be promising a targeting therapy for pancreatic cancer.