Abstract
In order to systematically evaluate the influence of lymph nodes (LNs) in lymph node metastases (LNM) of hepatocellular carcinoma (HCC), we set up a new in vitro model in which Hca-F and Hca-P cells were cultured in medium containing lymph node homogenates (LNHs). Differential protein expression was measured by two-dimensional gel electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI TOF/TOF MS). Results from protein identification revealed two metastatic correlative proteins, 78-kDa glucose-regulated protein (GRP78) and galectin-3 (GAL3). Western blotting confirmed that GRP78, a protein positively correlated with metastasis, increased 2.4-fold in Hca-F cells but decreased to almost a half in Hca-P cells (P<0.05). However, GAL3, a protein negatively correlated with metastasis, was decreased by a half in Hca-F cells but slightly increased non-significantly in Hca-P cells. Thus, our results reveal that some components of LNHs may facilitate a permissive environment for cancer cells with high metastasis potential to eventually metastasize. GRP78 and GAL3 may serve as potential biomarkers for the diagnosis of LNM in HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors and the third leading cause of cancer mortality worldwide [1]
These lines of evidence suggest that following incubation with lymph node homogenate (LNH) the high metastatic potential cell line was induced to regulate protein expression in favor of metastases, but the low metastatic potential cell line was induced in an opposite trend against metastasis
LNHs change the proteomic profiling in Hca‐F cells
Summary
Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors and the third leading cause of cancer mortality worldwide [1]. Hca‐F and Hca‐P cells are gynogenetic HCC cell lines generated from mice They are well‐characterized with different metastasis potentials exclusive to lymph nodes when inoculated subcutaneously in 615 mice. The major cellular components include fibroblasts, hepatic stellate cells, immune cells and endothelial cells These cells produce the non‐cellular components including the extracellular matrix (ECM) proteins, inflammatory cytokines, proteolytic enzymes and growth factors, which modulate the biological behavior of HCC by their effects on cancer signaling pathways in tumor cells and markedly impact tumor invasion and metastasis [8]. LNM is a dynamic process and one limitation of such studies (or the platform for such studies) is that the active changes related to LNM were not revealed It would be necessary in the process of HCC cells encountering the lymphatic environment and growing with lymph node components. We used an in vitro model where HCC cells with varying metastasis potential were grown with lymph node components in order to gain an insight into the possible and favorable LN niche condition(s) for metastasis
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