Stromal fibroblasts in the microenvironment of gastric carcinomas promote tumor metastasis via upregulating TAGLN expression.

BACKGROUND: Fibroblasts play a critical role in tumorigenesis, tumor progression and metastasis. However, their detailed molecular characteristics and clinical significance are still elusive. TAGLN is an actin-binding protein that plays an important role in tumorigenesis.

RESULTS: We investigated the interaction between cancer cells and the tumor microenvironment to determine how the fibroblasts from human gastric carcinoma facilitate tumorigenesis through TAGLN. QRT-PCR and Western blot indicated that TAGLN expression was upregulated in gastric carcinoma-associated fibroblasts (CAFs) that promote gastric cancer cell migration and invasion. Using small interfering RNA (siRNA), we found that CAFs enhanced tumor metastasis through upregulated TAGLN in vitro and in vivo. The expression of matrix metalloproteinase-2 (MMP-2) was significantly lower after TAGLN knock-down by siRNA. TAGLN levels were elevated in human gastric cancer stroma than normal gastric stroma and associated with differentiation and lymph node metastasis of gastric cancer.

CONCLUSION: CAFs may promote gastric cancer cell migration and invasion via upregulating TAGLN and TAGLN induced MMP-2 production.