title: Effect of junctional adhesion molecule-2 expression on cell growth, invasion and migration in human colorectal cancer.
abstract: The junctional adhesion molecule (JAMs) family belongs to the immunoglobulin subfamily involved in the formation of tight junctions (TJ) in both endothelial and epithelial cells. Aberrant expression of JAM-2 is associated with cancer progression but little work has been carried out in discovering how this affects changes in cell behaviour. The present study aimed to examine the expression of JAM-2 in human colon cancer specimens and cell lines and its role in the development of colon cancer. JAM-2 expression in human colon cancer specimens (normal, n=75; cancer, n=94) and cell lines was analysed using quantitative real-time PCR and conventional RT-PCR. Colon cancer cells were stably transfected with a mammalian expression vector to overexpress JAM-2-Flag. The effect on growth, adhesion and migration following overexpression of JAM-2 was then investigated using in vitro models. TJ function was assessed using a trans-epithelial resistance assay (TER, with an EVOM voltammeter). JAM-2 was lowly expressed in colon cancer cells such as RKO, HT115. JAM-2 overexpression in RKO cells (RKO-JAM-2) and HT115 cells (HT115-JAM-2) showed retarded adhesion (P<0.05). An in vivo tumour model showed that RKO-JAM-2 had significantly reduced growth (P<0.05), invasion (P<0.05) and migration (P<0.05) as well as in HT115-JAM-2, except on proliferation and migration. Expression of JAM-2 resulted in a significant increase in TER and decrease in permeability of polarized monolayers (P<0.05). Further analysis of JAM-2 transcript levels against clinical aspects demonstrated that the decreasing JAM-2 expression correlated to disease progression, metastasis and poor survival. Taken together, JAM-2 may function as a putative tumour suppressor in the progression and metastasis of colorectal cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Huishan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Hefen
authors.initials: H
authors.lastname: Yu
authors.affiliation: Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Cancer Institute of Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D015815:Cell Adhesion Molecules / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019108:Tight Junctions / Q000378:metabolism; D062765:Junctional Adhesion Molecule B
chemical_list: D015815:Cell Adhesion Molecules; C411887:JAM2 protein, human; D062765:Junctional Adhesion Molecule B