Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma.
Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma.
复制标题
肿瘤微环境中的肥大细胞促进了胰腺导管腺癌的体内生长。
DOI：
10.1158/1078-0432.ccr-11-0607
复制
发表时间：
2011-11-15
期刊：
影响因子：
--
通讯作者：
Hwu P
中科院分区：
文献类型：
--
作者：
Chang DZ;Ma Y;Ji B;Wang H;Deng D;Liu Y;Abbruzzese JL;Liu YJ;Logsdon CD;Hwu P
胰腺导管腺癌（PDAC）是癌症死亡的主要原因之一。由于对PDAC生长和发育的机制缺乏了解，目前尚无有效的治疗方法。炎症细胞，特别是肥大细胞，已被证明在某些癌症中起关键作用。我们进行了这项研究，以测试的假设，肥大细胞在肿瘤微环境是必不可少的PDAC肿瘤发生。在PDAC的自发小鼠模型（K-rasG 12 V）中确定在PDAC发展的各个阶段炎性细胞的存在。肥大细胞的重要性，确定使用原位植入PDAC细胞在肥大细胞缺陷型Kitw-sh/w-sh小鼠，并进一步证实了野生型骨髓来源的肥大细胞的重建。通过将肥大细胞的存在与PDAC患者的临床结局相关联来评估临床相关性。在PDAC（K-rasG 12 V）的自发小鼠模型中，存在肥大细胞向肿瘤微环境的早期流入。PDAC肿瘤生长在肥大细胞缺陷型Kitw-sh/w-sh小鼠中，但当将PDAC细胞注射到用野生型骨髓来源的肥大细胞重建的肥大细胞缺陷型小鼠中时，恢复了侵袭性PDAC生长。肥大细胞浸润到肿瘤微环境中是PDAC患者预后不良的预测因素。肥大细胞在小鼠模型的PDAC生长和发育中起重要作用，并且指示人类的不良预后，这使其成为潜在的新治疗靶点。
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. No effective therapy is currently available for PDAC because of the lack of understanding of the mechanisms leading to its growth and development. Inflammatory cells, particularly mast cells have been shown to play key roles in some cancers. We carried out this study to test the hypothesis that mast cells in the tumor microenvironment are essential for PDAC tumorigenesis. The presence of inflammatory cells at various stages of PDAC development was determined in a spontaneous mouse model of PDAC (K-rasG12V). The importance of mast cells was determined using orthotopically implanted PDAC cells in mast cell-deficient Kitw-sh/w-sh mice and further confirmed by reconstitution of wild-type bone marrow-derived mast cells. Clinical relevance was assessed by correlating the presence of mast cells with clinical outcome in patients with PDAC. In the spontaneous mouse model of PDAC (K-rasG12V), there was an early influx of mast cells to the tumor microenvironment. PDAC tumor growth was in mast cell-deficient Kitw-sh/w-sh mice, but aggressive PDAC growth was restored when PDAC cells were injected into mast cell-deficient mice reconstituted with wild-type bone marrow-derived mast cells. Mast cell infiltration into the tumor microenvironment was predictive of poor prognosis in patients with PDAC. Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target.