Overexpression of platelet-derived growth factor-B increases the growth, invasion, and angiogenesis of gastric carcinoma cells through protein kinase B

Abstract

Platelet-derived growth factor-B (PDGF-B) promotes tumor metastasis by inducing tumor cell growth, invasion, and angiogenesis in several cancers. However, the roles of PDGF-B in gastric carcinoma are largely unknown. We established two gastric carcinoma cell lines, SGC7901 and BGC823, to stably overexpress PDGF-B by lentiviral vectors, and determined their growth, invasion and angiogenesis. Overexpression of PDGF-B significantly enhanced the cell proliferation, invasion and angiogenesis of both SGC7901 and BGC823 cells, accompanied with increased activation of AKT, which is a downstream target of PDGF signaling pathway. Consequently, an AKT kinase inhibitor abolished the PDGF-B overexpression-mediated up-regulation of growth, invasion and angiogenesis. These results indicate that PDGF-B signaling may promote the metastasis of gastric carcinoma through AKT signaling. Targeting the PDGF-B pathway may be an alternative strategy for the development of therapies for gastric cancers.

Expression and prognostic significance of PDGF ligands and receptors across soft tissue sarcomas

“…PDGF modulates the growth, survival and cell function in several types of connective tissue cell. 17 In humans, PDGF oncogenic role has been reported in several cancers [7][8][9][10] such as gastric adenocarcinomas, 8 gliomas, 9,18 medulloblastomas, 19 DFSP and a subset of GIST, suggesting that it contributes to oncogenesis in these models and therefore may constitute a promising therapeutic target. 10 In human gastric cancers, high levels of PDGFA correlate with high-grade carcinomas and reduced patient survival.…”

“…5,6 Platelet-derived growth factor receptor (PDGFR) and its ligand PDGF have been proposed to play an important role in the growth of several cancers. [7][8][9][10] Genomic alterations of PDGFB and PDGFRA genes are therefore well documented in dermatofibrosarcoma protuberans (DFSP) and subsets of gastrointestinal stromal tumors (GISTs), with translocation and nonsynonymous mutations as key oncogenic events. Not only the discovery of these genetic alterations has been helpful to identify targeted treatments (imatinib), but it is also useful as prognostic and predictive parameters (in particular for GIST).…”

Assessment of PDGFRβ promoter methylation in canine osteosarcoma using methylation‐sensitive high‐resolution melting analysis

“…The pathogenic role of PDGF/PDGFR aberrant expression is much more evident in epithelial and neuroendocrine tumours than in mesenchymal tumours where their expression is inherently high, such as in their respective healthy tissues. In humans, a pivotal role of PDGFRβ activation has been demonstrated in gliomas and glioblastomas, malignant melanomas, gastric cancer, breast cancer, colorectal carcinomas, pancreatic neuroendocrine tumours, lung cancer and liposarcomas 17–27 . Overexpression and/or aberrant expression of PDGFRs may be because of different mechanisms, either acting at a transcriptional or post‐transcriptional level.…”

“…In humans, a pivotal role of PDGFRβ activation has been demonstrated in gliomas and glioblastomas, malignant melanomas, gastric cancer, breast cancer, colorectal carcinomas, pancreatic neuroendocrine tumours, lung cancer and liposarcomas. [17][18][19][20][21][22][23][24][25][26][27] Overexpression and/or aberrant expression of PDGFRs may be because of different mechanisms, either acting at a transcriptional or post-transcriptional level. The former may be modulated by epigenetic factors, such as the promoter methylation status or by genetic factors which account for somatic mutations and gene amplification/deletion.…”

Dapper homolog 1 alpha suppresses metastasis ability of gastric cancer through inhibiting planar cell polarity pathway

“…Promoter methylation is considered as an important hallmark of the progression and metastasis of gastric cancer. So far, many methylated genes have been identified play important roles in cell proliferation, cell cycle, apoptosis, angiogenesis, metastasis, thus contributing to the development of gastric cancer [6–10]. …”