Both of these studies suggested that HER2 positivity was associated with hepatic metastasis from GC specifically and was negatively associated with peritoneal metastasis. preventing and treating distinct metastases. We reviewed articles related to the molecular landscape of hematogenous metastasis from GC. hybridization; GC: Gastric cancer. Open in a separate window Figure 1 Schema of molecules associated with each step of the establishment of hepatic metastasis from gastric cancer. VIM: Vimentin; GPR155: G protein-coupled receptor 155; HIF-1: Hypoxia inducible factor-1 alpha; EGFL7: Epidermal growth factor-like domain-containing protein 7; CXCL1: C-X-C motif chemokine ligand 1; TIMP1: Tissue inhibitor of metallopeptidase 1; NFKB1/p105: Nuclear factor kappa B subunit 1; MAP1LC3: Microtubule associated protein 1 light chain 3; BECN1: Beclin1; SQSTM1/p62: Sequestosome 1; MFSD4: Major facilitator superfamily domain containing 4; PAK1: P21 (RAC1) activated kinase 1; VEGF-D: Vascular endothelial growth factor-D; TYMP: Thymidine phosphorylase. GC is the third leading cause of cancer-related death in both sexes worldwide[8]. The prognosis of patients with GC is dismal: The 5-year survival for all patients is approximately 50% and is only 25%-30% for patients with advanced GC due to a lack of curative therapeutic agents and sensitive biomarkers predicting recurrence[9]. Concerning peritoneal dissemination that is the most frequent metastasis from GC, development of recent therapeutic strategies might improve the prognosis of GC patients[10,11]. Surgical resection of hepatic metastasis can improve the outcome of GC patients, though the adaptation of surgical treatment for hematogenous metastasis is limited[12]. The development of remedies against hematogenous metastasis has stalled. Elucidating the molecular biological mechanisms specific for hematogenous metastasis from GC will be a significant and effectual step for the development of novel biomarkers and therapeutic target molecules, which will lead to the improvement of patients prognoses. EPITHELIAL MESENCHYMAL TRANSITION Procaterol HCl AND INVASION INTO THE CIRCULATION Epithelial mesenchymal transition and invasion into the circulation are the first steps for distant metastasis from the primary lesion. To spread to other organs through the blood stream, tumor cells must invade the basal lamina, reach and invade vessels, and detach from the primary tumor nodule. Then, single tumor cells or tumorspheres must acquire a mesenchymal phenotype and resist anoikis to arrive at a target organ. We have listed the genes that reportedly contribute to these steps and summarized the studies below. Vimentin Vimentin (VIM) is a type III intermediate filament protein that is mainly expressed in mesenchymal cells and an important marker of epithelial mesenchymal transition (EMT)[13]. Epithelial cancer cells acquire motility and metastatic potential by cellular re-programming to a mesenchymal phenotype. Increased vimentin expression has been reported in various cancers including gastrointestinal cancers[14,15]. Zhao et al[16] explored the clinical significance of VIM expression and human epidermal growth factor receptor 2 (HER2) status in GC tissues by immunohistochemistry (IHC). They found that VIM expression was significantly correlated with older age, advanced stage, poorly differentiated type, venous invasion, hepatic metastasis and recurrence and that HER2 status was correlated with advanced cancer, poor differentiation, venous invasion, hepatic metastasis and recurrence. There was a significant correlation between VIM expression and HER2-positivity. VIM expression was detected in 9.8% in GC patients and was not detected in early Procaterol HCl GC patients. The 3-year survival of the patients with vimentin-positive GC was significantly poorer than that of patients with vimentin-negative GC. VIM positivity was an independent prognostic factor in multivariate analysis with respect to overall survival. VIM plays an important role in metastasis and may have a more requisite role in the establishment of hematogenous metastasis in GC. EMT inhibitors including TGF- signaling pathway inhibitor might be a therapeutic agent for hematogenous metastasis from GC[17]. G protein-coupled receptor 155 G protein-coupled receptors (activates the G protein and intracellular signaling. Because there are numerous and Procaterol HCl they are the Rabbit polyclonal to ZNF544 origin of many intracellular signals, represent 30%-50% of the targets of currently marketed therapeutic drugs[19]. is a member of the family and little is known about its function. Our recent global expression analysis of primary GC tissues obtained from.
Both of these studies suggested that HER2 positivity was associated with hepatic metastasis from GC specifically and was negatively associated with peritoneal metastasis