Metastasis of cancer cells is a major cause of death in cancer patients. The process of cancer metastasis includes the proliferation of primary cancer cells, local invasion, intravasation and cancer cell survival in blood flow, extravasation and attachment to secondary organs and metastatic growth in a new environment. In these mechanisms of cancer metastasis, CXC chemokine receptor 4 (CXCR4) and its ligand play an important role. Stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is well known as a ligand of CXCR4, and macrophage migration-inhibitory factor (MIF) has recently become known as a ligand of CXCR4. In many types of cancers including breast, pancreatic and colorectal cancer (CRC), CXCR4/SDF-1α has been investigated in metastasis-related cancer behavior, which include cell proliferation, adhesion, migration and invasion. However, CXCR4/MIF has rarely been investigated in the metastatic behavior of colon cancer cells. In this report, the effect of SDF-1α or MIF was studied on cell cycle, cell proliferation, adhesion and migration of the CXCR4-expressing colon cancer cell line SW480. SDF-1α or MIF caused a decrease in the number of cells in G0/G1 phase and an increase in the numbers of cells in S and G2/M phases. In addition, SDF-1α or MIF caused an increase in cell proliferation, cell adhesion to fibronectin and migration. AMD3100, a CXCR4 antagonist, attenuated these effects, which included increased cell proliferation, adhesion and migration due to treatment of CXCR4-expressing colon cancer cells with SDF-1α or MIF. In conclusion, SDF-1α or MIF affects the metastasis-related behaviors of CXCR4-expressing colon cancer cells.
Background PDX model (Patient-derived xenograft model), one of the several advanced techniques for researching cancer, have appeared to overcome and supplement limitation of cell line based cancer research techniques. Purpose/ Methods To observe variation of gene level during organ-specific metastasis in breast cancer patients, we made PDX model after transplanting primary tissues from TNBC breast cancer patients to NOG-SCID mouse. Then we performed RNA sequencing and analyzed mRNA expression dataset using both metastatic tissues of axillary lymph node and tissues from xenograft tumor which was grown in mouse fat fad. Using breast cancer cell lines, selected genes from RNA sequencing and mRNA array dataset were examined their expression level by RT-PCR and qRT-PCR techniques. In addition, migration ability was also confirmed by migration assay in each cell line. Results TMSB4X, ANXA2P2, RPLP1 and IGFBP2 were more expressed in LN metastatic tissues than primary tissues and MGP, PROM1, MIA, KRT17 and KRT15 were downregulated in LN metastatic tissues. As a result of RT-PCR, qRT-PCR and migration assay, we knew that TMSB4X, ANXA2P2 and RPLP1 were mostly expressed in 14 breast cancer cell lines except some cell lines, and MIA was highly expressed in TNBC cell lines except MDA-MB-453. In addition, Hs578T, MDA-MB-231, HCC70, HCC38 and BT20 cell line had much higher migration ability than other cell lines. Discussion PDX model, generated by tissues from breast cancer patients, represents similar changes of gene expression or mutation as compared with the patients. In addition, PDX model can preserve gene expression patterns and mutation profiles. Therefore, candidate gene screening for lymph node metastasis in PDX model is a meaningful process for applying clinical study. Tumor metastasis ability is usually determined by migration or invasion ability of cancer cells, and specific signaling pathways that related to migration or invasion are also important to tumor metastasis mechanisms. Citation Format: Hyeong-Gon Moon, Hyun Hye Moon, Wonshik Han, Dong-Young Noh. Lymph node metastasis-related genes discovered through patient-derived xenograft models. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-08.
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