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肿瘤细胞与源自人类骨髓的培养基质细胞之间的相互作用。

Interaction of tumour cells with cultured stromal cells from human bone marrow.

作者信息

Joling P, Rademakers L H, Verdaasdonk M A, Zimmermann D, Spierings D C, Werner N, de Weger R A, van den Tweel J C

机构信息

Department of Pathology, University Hospital, Utrecht, The Netherlands.

出版信息

Thymus. 1994;23(2):115-26.

PMID:7536964
Abstract

Adhesion of tumour cells to cultured bone marrow stromal cells has been studied in an in vitro model system. Stromal cells were isolated from bone marrow aspirates. Immunohistochemical and electron microscopical analysis revealed a uniform cell monolayer of myofibroblastic cells, expressing fibroblast antigens and smooth muscle actin. Cell interactions with tumour cells lines showed different patterns. The K562 cells bound in low numbers to stromal cells. HEL-DR- and HL60 cells adhered to stromal cells showing an enlarged cell contact area (spreading) attenuated by distinct contact sites and they invaded the monolayer. Adhesion molecules, important for cell contacts, were detected on tumor cells. Different VLA antigens were detected on tumour cells, but on stromal cells only VLA-5 and CD29 were found. In vitro inhibition studies with mAbs against adhesion molecules indicated two major pathways for binding of tumour cells to stromal cells: VCAM-1/VLA-4 and fibronectin/VLA-5. Variation in inhibition of mAbs to VLA-4 and VCAM-1 indicated the existence of critical epitopes in the adhesion of tumour cells.

摘要

在体外模型系统中研究了肿瘤细胞与培养的骨髓基质细胞的黏附情况。从骨髓抽吸物中分离出基质细胞。免疫组织化学和电子显微镜分析显示,肌成纤维细胞形成均匀的细胞单层,表达成纤维细胞抗原和平滑肌肌动蛋白。细胞与肿瘤细胞系的相互作用表现出不同模式。K562细胞与基质细胞的结合数量较少。HEL-DR和HL60细胞黏附于基质细胞,表现出扩大的细胞接触面积(铺展),但被不同的接触位点减弱,并且它们侵入了单层。在肿瘤细胞上检测到对细胞接触很重要的黏附分子。在肿瘤细胞上检测到不同的VLA抗原,但在基质细胞上仅发现VLA-5和CD29。用针对黏附分子的单克隆抗体进行的体外抑制研究表明,肿瘤细胞与基质细胞结合的两条主要途径:VCAM-1/VLA-4和纤连蛋白/VLA-5。针对VLA-4和VCAM-1的单克隆抗体抑制作用的差异表明,肿瘤细胞黏附中存在关键表位。

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