Abstract
A high serine content in body fluid was identified in a portion of patients with gastric cancer, but its biological significance was not clear. Here, we investigated the biological effect of serine on gastric cancer cells. Serine was added into the culture medium of MGC803 and HGC27 cancer cells, and its influence on multiple biological functions, such as cell growth, migration and invasion, and drug resistance was analyzed. We examined the global transcriptomic profiles in these cultured cells with high serine content. Both MGC803 and HGC27 cell lines were originated from male patients, however, their basal gene expression patterns were very different. The finding of cell differentiation-associated genes, ALPI, KRT18, TM4SF1, KRT81, A2M, MT1E, MUC16, BASP1, TUSC3, and PRSS21 in MGC803 cells suggested that this cell line was more poorly differentiated, compared to HGC27 cell line. When the serine concentration was increased to 150mg/ml in medium, the response of these two gastric cancer cell lines was different, particularly on cell growth, cell migration, and invasion and 5-FU resistance. In animal experiment, administration of high concentration of serine promoted cancer cell metastasis to local lymph node. Taken together, we characterized the basal gene expressing profiles of MGC803 and HGC27. The HGC27 cells were more differentiated than MGC803 cells. MGC803 cells were more sensitive to the change of serine content. Our results suggested that the responsiveness of cancer cells to microenvironmental change is associated with their genetic background.
Highlights
Gastric cancer (GC), which ranks the fifth in incidence and the third in mortality worldwide, is one of the most common malignant tumors of digestive tract
We explored the influence of high serine concentration on multiple biological behaviors, as well as the possible molecular mechanisms for GC
After incubating MGC803 or HGC27 cells with the above five mediums for 24 h, the medium with 150 mg/ml serine showed the highest effect in promoting cell migration (69.2 ± 5.4) compared to that in RPMI1640 medium (28.8 ± 5.3) in HGC27 cells (P
Summary
Gastric cancer (GC), which ranks the fifth in incidence and the third in mortality worldwide, is one of the most common malignant tumors of digestive tract. This malignancy commonly occurs in Asian countries, especially in China, Japan, and South Korea (Torre et al, 2015; Bray et al, 2018). In a previous study on urine metabolites, a group of amino acids were found to be abnormally elevated in GC patients than that in healthy controls. Those amino acids include alanine, glycine, valine, serine, isoleucine, threonine, proline, methionine, tyrosine, and tryptophan. These findings implied that increased certain amino acids in body fluid might have biological significance on GC development
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