Daly Aisling J, McIlreavey Leanne, Irwin Chris R
Oral Science Research Group, Queen's University School of Medicine and Dentistry, Royal Victoria Hospital, Grosvenor Road, Belfast, United Kingdom.
Oral Oncol. 2008 Jul;44(7):646-51. doi: 10.1016/j.oraloncology.2007.08.012. Epub 2007 Nov 9.
Invasion and metastasis of oral squamous cell carcinoma (OSCC) is dependent on signals received from stromal fibroblasts present in the surrounding connective tissue. The aim of this study was to investigate the regulation of expression of two important signaling molecules--HGF and SDF-1--by both stromal fibroblasts and their 'activated' form, myofibroblasts, and to determine the role of these two factors in stimulating OSCC cell invasion in vitro. Fibroblasts and myofibroblasts produced similar levels of HGF and SDF-1. IL-1alpha and OSCC cell conditioned medium both stimulated HGF and SDF-1 expression, while TGF-beta(1) inhibited production of each factor. Myofibroblast-derived conditioned medium stimulated OSCC cell invasion through matrigel. Blocking antibodies to both HGF and SDF-1 reduced the level of invasion. In fibroblast-free organotypic raft cultures, addition of HGF and SDF-1 stimulated OSCC cell invasion into the underlying collagen gel, although the pattern of invasion differed from that induced by fibroblasts. Fibroblast-derived HGF and SDF-1 appear to play central roles in the reciprocal interactions between OSCC cells and underlying stromal fibroblasts leading to the local invasion of oral cancer.
口腔鳞状细胞癌（OSCC）的侵袭和转移依赖于从周围结缔组织中的基质成纤维细胞接收的信号。本研究的目的是调查基质成纤维细胞及其“活化”形式肌成纤维细胞对两种重要信号分子——肝细胞生长因子（HGF）和基质细胞衍生因子-1（SDF-1）表达的调控，并确定这两种因子在体外刺激OSCC细胞侵袭中的作用。成纤维细胞和肌成纤维细胞产生的HGF和SDF-1水平相似。白细胞介素-1α（IL-1α）和OSCC细胞条件培养基均刺激HGF和SDF-1的表达，而转化生长因子-β1（TGF-β1）抑制每种因子的产生。肌成纤维细胞衍生的条件培养基刺激OSCC细胞通过基质胶侵袭。针对HGF和SDF-1的阻断抗体降低了侵袭水平。在无成纤维细胞的器官型筏培养中，添加HGF和SDF-1刺激OSCC细胞侵入下层胶原凝胶，尽管侵袭模式与成纤维细胞诱导的不同。成纤维细胞衍生的HGF和SDF-1似乎在OSCC细胞与下层基质成纤维细胞之间的相互作用中发挥核心作用，导致口腔癌的局部侵袭。
