Abstract
(1) Background: stromal-derived factor-1 (SDF-1/CXCL12), hepatocyte and vascular-endothelial growth factors (HGF and VEGF) have been shown to facilitate cell motility, proliferation and promote local tumor progression and metastatic spread. Recent research shows the important role of these cytokines in gastric cancer (GC) progression. (2) Methods: 21 gastric cancer patients and 19 healthy controls were included in the study. SDF-1, HGF and VEGF levels were evaluated in sera by ELISA. Patients and control sera were used to stimulate CRL-1739 GC cell line, and chemotaxis, adhesion and proliferation potential were assessed. (3) Results: Concentrations of SDF-1, HGF and VEGF were significantly higher in patients than in controls. Chemotaxis and adhesion assays revealed a significant response of GC cells to patients’ serum. Furthermore, significant relationships were seen between chemotactic/adhesion response and tumor stage. Serum from intestinal early GC patients produced significantly stronger chemotactic response when compared to patients with metastatic spread. In turn, serum from patients with distal metastases significantly increased the adhesion of GC cells when compared to sera from the patients with no distal metastases. We also observed that HGF strongly stimulated the proliferation of CRL-1739 cells. (4) Conclusions: We observed that the sera from GC patients, but also SDF-1, HGF and VEGF used alone, have a strong pro-metastatic effect on CRL-1739 cells. We also demonstrated that the concentration of these cytokines is specifically elevated in the sera of patients in an early stage of malignancy. Our results indicate that SDF-1, HGF and VEGF are very important molecules involved in gastric cancer progression.
Highlights
Despite recent progress in diagnostic techniques, gastric cancer (GC) remains a clinical problem and a challenge for clinicians and scientists
Recent studies have shown that the serum concentration of SDF-1, HGF, and VEGF is elevated in patients with several types of cancers, including breast, liver or ovarian cancer [29–31], and what is important is that it was shown that GC tumor mass secretes VEGF and it may serve as biomarker for disease progression and remission [32,33]
We report that the serum from GC patients, SDF-1, HGF and VEGF, have pro-metastatic effects on the GC CRL-1739 cell line
Summary
Despite recent progress in diagnostic techniques, gastric cancer (GC) remains a clinical problem and a challenge for clinicians and scientists. GC cells are characterized by an unusual ability to incite the cooperation with other cell types, like fibroblasts, monocytes, endothelial progenitor cells and endothelial cells This cooperation, instead of protecting from the pathological phenotype, leads to growth promotion, angiogenesis and migration [10,15–17]. This process involves the interaction of several factors—including VEGF, tumor necrosis factor alpha (TNF-α), HGF, epidermal growth factor (EGF) and matrix metalloproteinases (MMPs)—released by both the recruited cells and GC cells. Recent studies have shown that the serum concentration of SDF-1, HGF, and VEGF is elevated in patients with several types of cancers, including breast, liver or ovarian cancer [29–31], and what is important is that it was shown that GC tumor mass secretes VEGF and it may serve as biomarker for disease progression and remission [32,33]
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