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Abstract
Background Cancer-associated fibroblasts (CAFs) play a pivotal role in promoting tumour progression by secreting a variety of growth factors. Among these secreted proteins, thrombospondin-2 (THBS2) is recognized as a significant prognostic indicator in various cancers. However, to date, few studies on the role of THBS2 in gastric cancer (GC) progression have been reported.
Methods THBS2 expression was shown to be abnormally elevated in GC by combined transcriptomic and proteomic sequencing of GC tissues. The association between THBS2 expression and clinical outcomes of GC patients was evaluated. Primary CAFs and normal fibroblasts (NFs) were extracted from tumour tissues and paracarcinoma nontumor tissues of patients with GC. These primary cells were used to investigate the effect of CAF on the biological behavior of GC cells, which promotes GC cell metastasis. RNA sequencing was subsequently conducted to preliminarily elucidate the downstream molecular regulatory mechanism by which THBS2 promotes the metastasis of GC cells.
Results THBS2 was aberrantly expressed in the stromal components of primary GC tumour tissues with lymph node metastases (IDDF2024-ABS-0370 Figure 1). The expression level of THBS2 was significantly proportional to the depth of invasion, the number of lymph node metastases, and the disease stage of gastric cancer, and predicted poor survival rate of patients after surgery (IDDF2024-ABS-0370 Figure 1). THBS2 secreted by CAF could promote the proliferation and metastasis of GC cells in vivo and in vitro (IDDF2024-ABS-0370 Figure 2). THBS2 could bind to CD36 protein on the membrane of GC cells, then activate its downstream Akt/Erk signalling pathway, which enhanced the invasion and metastasis abilities of GC cells (IDDF2024-ABS-0370 Figure 3).
Conclusions The mechanism by which THBS2 secreted by CAF cells promoted the metastasis of GC cells provided a new idea for molecular targeted therapy of GC.