Abstract
Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2), which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression.
Highlights
Cancer remains as a leading cause of death, accounting for 14.1 million new cases and 8.2 million deaths in 2012 [1]
A Pearson correlation analysis showed that NME2 expression was independently associated with rates of cell differentiation (r = 0.436, p = 0.000) and spread to the local lymph nodes (r = -0.281, p = 0.001, Table 1)
We have investigated the relationship between the NME2 expression and characteristics of gastric cancer in tissues surgically removed from patients and in cultured cells from two known gastric cancer lines
Summary
Cancer remains as a leading cause of death, accounting for 14.1 million new cases and 8.2 million deaths in 2012 [1]. Gastric cancer cells can directly spread to adjacent organs (local invasion) such as the pancreas, the transverse colon, the liver and the spleen as well as to remote lymph nodes, the lungs, and bone tissue. While being two different pathological processes, local invasion and remote metastasis are interconnected where the former often promotes and propagates the latter. Genetic mutations and their aberrant products are key hallmarks and enablers of cancer cells for proliferation, resistance to apoptosis, local invasion, metastasis, immune evasion, angiogenesis, and response to DNA damage.
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