Abstract
Gastric cancer (GC) is one of the most frequent malignant tumors worldwide and is associated with high invasiveness, high metastasis and poor prognosis. Cancer-associated fibroblasts (CAFs), residing around tumor cells in tumor stroma, are important modifiers of tumor initiation and progression. However, the molecular mechanisms by which CAF's modulate tumor development have yet not to be characterized in GC. Here we performed tissue assay analyses identifying that Lumican, an extracellular matrix protein, is highly expressed in human gastric CAFs and its expression is positively associated with depth of invasion, lymph node metastasis, TNM stage and poor survival rate of GC. Functional studies revealed that integrin β1-FAK signaling pathways mediate the promoting effect of Lumican on GC cell proliferation, migration and invasion in vitro. In accordance with these observations, in GC cells co-cultured with CAFs in which Lumican had been knocked down, decreased gastric tumor growth and metastasis in vivo was apparent. In summary, CAF-derived Lumican contributes to tumorigenesis and metastasis of GC by activating the integrin β1-FAK signaling pathway.
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