Abstract
IntroductionGastric cancer (GC) is one of the most frequent malignant tumours worldwide and is associated with high invasiveness, high metastasis and poor prognosis. Cancer-associated fibroblasts (CAFs), residing around tumour cells in tumour stroma, are important modifiers of tumour initiation and progression. However, the molecular mechanisms by which CAF’s modulate tumour development have yet not to be characterised in GC.Material and methodsCAFs and normal fibroblasts (NFs) were cultured from resected gastric cancer tissues and patient matching non-cancerous tissues. The expression of Lumican in gastric CAFs was detected by quantitative RT-PCR and Westerblot. The effects of CAFs, which was interfered with Lumican, on gastric cancer cell proliferation, migration and invasion in vitro were measured. were measured by CCK8, the coculture migration or matrigel invasion assay, respectively. In vivo tumorigenesis and metastasis were performed by injection CAFs and GC cells subcutaneously or peritoneally.Results and discussionsLumican, 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. Knockdown of Lumican in CAFs impaired the GC cell proliferation, migration and invasion in vitro, as well as tumorigenesis and peritoneal metastasis in vivo. Further functional studies revealed that integrin beta1-FAK signalling pathway mediated the promoting effects of stromal Lumican on GC cell metastasis potential.ConclusionCAF-derived Lumican contributes to tumorigenesis and metastasis of GC by activating the integrin b1-FAK signalling pathway.Targeting stromal Lumican may provide a potential treatment strategy for GC.
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