Interactions between microenvironment and cancer cells in two animal models of bone metastasis.

Interactions between microenvironment and cancer cells in two animal models of bone metastasis.
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在两个骨转移动物模型中,微环境与癌细胞之间的相互作用。

DOI:
10.1038/sj.bjc.6604238
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发表时间:
2008-02-26
影响因子:
8.8
通讯作者:
Chappard, D.
Chappard, D.
中科院分区:
医学1区
文献类型:
--
作者:
Blouin, S.;Basle, M. F.;Chappard, D.

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骨微环境中癌细胞的优先增殖特征不明显。研究了与溶骨性(步行者W256)和成骨细胞(MatLyLu MLL)转移瘤接触的骨髓和其他器官微环境的表达模式。Fisher和Copenhagen大鼠分别接受W256和MLL细胞注射。通过免疫化学分析骨和软组织的DKK 1、组织蛋白酶K、RANKL、MCSF或IL 6表达。抗酒石酸酸性磷酸酶(TRAcP)阳性细胞检测的组织酶技术。在骨中,MCSF和DKK 1的表达显示在骨髓基质细胞中,与两种肿瘤的转移灶接触。在肿瘤附近发现许多基质细胞RANKL阳性。发现表达组织蛋白酶K的细胞和多核TRAcP+细胞与骨小梁直接接触,但也存在于转移细胞附近的骨髓间隙中。在骨外肿瘤中,与恶性细胞接触的细胞不表达DKK 1、MCSF、组织蛋白酶K和IL 6。在皮下肿瘤的外周发现一些RANKL+细胞,但可能代表朗格汉斯细胞。在恶性细胞附近从未观察到TRAcP+细胞的异常存在。间质细胞和癌细胞之间的相互作用诱导的表达,导致破骨细胞只在骨微环境中的特点。
The preferential proliferation of cancer cells in the bone microenvironment is poorly characterised. Expression pattern of bone marrow and other organ microenvironment in contact with osteolytic (Walker W256) and osteoblastic (MatLyLu MLL) metastases were investigated. Fisher and Copenhagen rats received, respectively, W256 and MLL cells injection. Bone and soft tissues were analysed by immunochemistry for DKK1, cathepsin K, RANKL, MCSF or IL6 expression. Tartrate-resistant acid phosphatase (TRAcP)-positive cells were detected by a histoenzymatic technique. In bone, expressions of MCSF and DKK1 were shown in stromal cells of the bone marrow, in contact with metastatic foci of both tumours. Many stromal cells were found RANKL positive in the vicinity of the tumours. Cells expressing cathepsin K and multinucleated TRAcP+ cells were found in direct contact with trabeculae but also in bone marrow spaces near metastatic cells. In extraosseous tumours, cells in contact with malignant cells did not expressed DKK1, MCSF, cathepsin K and IL6. Some RANKL+ cells were found in the periphery of subcutaneous tumours but may represent Langerhans cells. Abnormal presence of TRAcP+ cells was never observed in the vicinity of malignant cells. Interaction between stromal and cancer cells induces the expression on the formers of characteristics leading to osteoclastogenesis only in the bone microenvironment.
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