Cancer metastasis, a complex and sequential network of cellular events involved in the migration and establishment of malignant cells from original site to distant foci, is an important and significant contributor to morbidity and mortality of cancer patients. Despite the clinical importance of cancer metastasis, its molecular and biochemical mechanism remains unclear. The identification of tumor suppressor gene confirmed that metastasis might involve the functional loss of genes that maintain the cellular differentiation optimally. Metastasis suppressor is defined by the ability to reduce the metastatic property of cancer cells without affecting its tumorigenesis. Since NM23 was first identified in 1988 as a metastasis suppressor, several metastasis suppressor genes have been identified and characterized. In this article, we review the complex and multi-step process of cancer metastasis and describe the recent progress of metastasis suppressors in the studies of identified. Consequently, we hope to introduce the new therapeutic target for the metastasis suppressors in cancer patients.
English Abstract ; *Genes, Tumor Suppressor ; Humans ; Neoplasm Metastasis/genetics/*physiopathology ; Nucleoside-Diphosphate Kinase/genetics/metabolism

Cell Movement ; drug effects ; Chemokine CXCL12 ; genetics ; metabolism ; pharmacology ; physiology ; Humans ; Neoplasm Invasiveness ; physiopathology ; Neoplasm Metastasis ; physiopathology ; Neoplasms ; metabolism ; Neovascularization, Pathologic ; physiopathology

Acetyltransferases ; genetics ; Breast Neoplasms ; genetics ; Female ; GPI-Linked Proteins ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Membrane Glycoproteins ; genetics ; Neoplasm Metastasis ; genetics ; physiopathology ; S100 Proteins ; genetics ; Transcription Factors ; genetics

Cell Movement ; genetics ; physiology ; Humans ; Microfilament Proteins ; genetics ; metabolism ; Models, Biological ; Neoplasm Metastasis ; genetics ; physiopathology ; Protein Binding ; genetics ; physiology ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Vesicular Transport Proteins ; genetics ; metabolism

OBJECTIVETo investigate the molecular mechanism of nectin-like molecule 1 (NECL1) inhibiting the migration and invasion of U251 glioma cells.

METHODSWe infected U251 glioma cells with adeno-nectin-like molecule 1 (Ad-NECL1) or empty adenovirus (Ad). Transwell and wound healing assays were performed to observe the migration of U251 cells incubated with the cell supernatant from Ad-NECL1 or Ad infected U251 cells. DNA microarray was applied to screen the gene expression profile after the restoration of NECL1 in U251 glioma cell lines. The differential expression of osteopontin (OPN), a gene related to migration and invasion, was further analyzed with semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry.

RESULTSThe restoration of NECL1 inhibited migration of U251 cells significantly (P<0.05). Altogether 195 genes were found differentially expressed by microarray, in which 175 were up-regulated and 20 down-regulated, including 9 extracellular matrix proteins involved in the migration of cells. Both mRNA and protein expressions of OPN, the most markedly reduced extracellular matrix protein, were found decreased in U251 cells after restoration of NECL1. Immunohistochemical assay also detected an increase of OPN in glioma tissues, related with the progressing of malignant grade.

CONCLUSIONA link might exist between NECL1 and the extracellular matrix protein OPN in inhibiting the migration and invasion of U251 glioma cells.

Brain Neoplasms ; metabolism ; pathology ; Cell Adhesion Molecules ; physiology ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; physiology ; Glioma ; metabolism ; pathology ; Humans ; Nectins ; Neoplasm Invasiveness ; physiopathology ; Neoplasm Metastasis ; physiopathology ; Osteopontin ; genetics

To evaluate the relationship between p27Kip1 low expression in breast cancer and its prognostic implication in breast carcinoma patients. Methods All data that were associated with the study of the relationship between p27Kip1 and the prognosis for breast cancer was pooled from Cochrane library, PubMed, Embase and Medlinebase. The outcome was measured using the risk ratio (RR). Data pooling was performed by RevMan 4. 2. Results 6457 patients from 20 studies were included in this meta-analysis. RR estimate of overall survival (OS) for patients with low level p27Kip1 was 2.07 [1.66,2.60] (P<0.01). For disease free survival (DFS), the pooled RR was 1.27 [1.10,1.47] (P<0.05). The combined RR estimate of relapse free survival (RFS) for patients with low level of p27Kip1 was 1.49 [0.92, 2.42] (P >0.05). In patients with lymph node negative breast carcinoma, the combined RR for OS and RFS were 1.98 [1.34,2.91] (P <0.01) and 1.28 [0.45,3.65] (P > 0.05), respectively. Among the patients with lymph node positive breast carcinoma, the combined RR for OS and RFS was 1.92 [1.31, 2.82] (P=0.0009) and 1.35 [0.96,1.89] (P>0.05) respectively. Conclusions Low level of p27Kip1 appears to be an independent prognostic factor to OS and DFS of breast cancer patients but not to RFS. Additional studies with large patient number and widely accepted practical methods are required to derive the precise prognostic significance of p27Kip1 expression in breast cancer patients.
Biomarkers, Tumor ; analysis ; Breast Neoplasms ; diagnosis ; genetics ; metabolism ; pathology ; Carcinoma ; diagnosis ; genetics ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; genetics ; metabolism ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Lymphatic Metastasis ; diagnosis ; physiopathology ; Neoplasm Staging ; methods ; Prognosis

Platelet-derived growth factors (PDGFs) and their receptors were identified and purified decades ago. PDGFs are important during normal development and in human cancers. In particular, autocrine PDGF signaling has been implicated in various types of malignancies such as gliomas and leukemia. In contrast, paracrine signaling was found in cancers that originate from epithelial cells, where it may be involved in stromal cell recruitment, metastasis, and epithelial-mesenchymal transition. This editorial briefly discusses autocrine and paracrine PDGF signaling and their roles in human cancers, and introduces a series of review articles in this issue that address the possible roles of PDGFs in various processes involved in different types of cancers.
Animals ; Autocrine Communication ; Epithelial-Mesenchymal Transition ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms ; pathology ; physiopathology ; Paracrine Communication ; Platelet-Derived Growth Factor ; genetics ; metabolism ; physiology ; Receptors, Platelet-Derived Growth Factor ; genetics ; metabolism ; physiology

OBJECTIVETo investigate the inhibitory effects of recombinant human endostatin (rh-ES) on cell adhesion, metastatic potential and invasiveness of hepatocellular carcinoma HCCLM6 cells in vitro.

METHODSThe changes in the cell proliferation status of HCCLM6 cells treated with different concentrations of rh-Endostatin in vitro was measured with MTT assay, and their invasiveness and migration were assayed using transwell cell culture chamber. The cell adhesion assay was carried out on 96-well plate precoated with matrigel.

RESULTSRh-ES showed inhibitory effect against the proliferation of HCCLM6 cells after a 72-h treatment. The adhesion, metastatic potential and invasiveness of the cells were obviously inhibited by rh-Endostatin in a dose-dependent manner.

CONCLUSIONRh-ES inhibits the adhesion, invasiveness and migration of hepatocellular carcinoma cells in vitro, and the mechanism needs further investigation.

Antineoplastic Agents ; pharmacology ; Carcinoma, Hepatocellular ; pathology ; physiopathology ; Cell Adhesion ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Endostatins ; genetics ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; physiopathology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Recombinant Proteins ; pharmacology

Celastrol is a type of quinone methyl triterpene isolated from traditional Chinese medicine Tripterygium wilfordii, with pharmacological activities, like anti-inflammatory, immunosuppression and anti-tumor. This study focused on the effects of celastrol on adhesion, migration and invasion of lung cancer cells. The migration inhibition of lung cancer cells induced by celastrol was detected by the scratch test. The invasion inhibition of lung cancer cells induced by celastrol was measured by the transwell experiment. RT-PCR and Western blot were used to determine the effect of different concentrations of celastrol in integrin family and Akt signaling pathway in lung cancer cells. The results showed that celastrol inhibited adhesion, migration and invasion of lung cancer cells and expressions of integrins β3, β4, αv and phosphorylated Akt, GSK-3β, c-Raf, PDK1 in Akt signal pathway in a dose-dependent manner. Therefore, the study implies that Celastrol could inhibit the metastasis of lung cancer cells by suppressing Akt signaling pathway and expression of integrins.
Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Integrins ; genetics ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; pathology ; physiopathology ; Neoplasm Metastasis ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Signal Transduction ; drug effects ; Triterpenes ; pharmacology

Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction (SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods. α-amyrin and betulinic acid contents of SF-3 were measured by HPLC methods. Fluorescent assays revealed characteristic apoptotic features, including cell shrinkage, nuclear condensation, and marked decrease in mitochondrial membrane potential in SF-3 treated cells. In addition, increased levels of caspases-9 and -3/7 levels were also observed in SF-3 treated cells. SF-3 showed promising antimetastatic properties in multiple in vitro assays. Multi-pathway analysis revealed significant down-regulation of WNT, HIF-1α, and EGFR with simultaneous up-regulation of p53, Myc/Max, and TGF-β signalling pathways in SF-3 treated cells. In addition, promising growth inhibitory effects were observed in SF-3 treated HCT 116 tumour spheroids, which give a hint about in vivo antitumor efficacy of SF-3 phytoconstituents. In conclusion, these results demonstrated that anticancer effects of SF-3 towards colon cancer are through modulation of multiple molecular pathways.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Colorectal Neoplasms ; drug therapy ; metabolism ; pathology ; physiopathology ; ErbB Receptors ; genetics ; metabolism ; HCT116 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Magnoliopsida ; chemistry ; Neoplasm Metastasis ; prevention & control ; Plant Bark ; chemistry ; Plant Extracts ; pharmacology ; Signal Transduction ; drug effects ; Wnt Proteins ; genetics ; metabolism