Claudin-4 expression is associated with tumor invasion, MMP-2 and MMP-9 expression in gastric cancer

Published on Sep 1, 2010in Experimental and Therapeutic Medicine1.785
· DOI :10.3892/ETM.2010.116
Tsann-Long Hwang30
Estimated H-index: 30
(Memorial Hospital of South Bend),
Li-Yu Lee44
Estimated H-index: 44
(Memorial Hospital of South Bend)
+ 3 AuthorsChi-Ming Wu10
Estimated H-index: 10
(VNU: Vanung University)
: Claudin-4 is a member of the claudin family, a large family of transmembrane proteins that are essential in the formation and maintenance of tight junctions. Matrix metal-loproteinase (MMP)-2 and -9 degrade type IV collagen of the extracellular matrix and basal membranes. Claudin-4 activates MMP-2, indicating that claudin-mediated increased cancer cell invasion may result from the activation of MMP proteins. In the present study, we used immunohistochemistry to examine the expression levels of claudin-4, MMP-2 and MMP-9 in 189 gastric cancer samples, and analyzed their correlation with tumor invasion, clinicopathologic parameters and clinical outcome. The relationship between claudin-4 expression and MMP-2 and -9 expression was also investigated. The expression of claudin-4 was found to be significantly higher in gastric cancer cases with advanced depth of wall invasion, lymph node metastasis, lymphatic invasion and higher TNM stage. Further analysis revealed claudin-4 expression to be significantly correlated with the expression of MMP-2 and -9. Kaplan-Meier survival analysis indicated that MMP-9 expression was correlated with poor prognosis. These results suggest that claudin-4 expression is associated with tumor invasion and with MMP-2 and -9 expression in gastric cancer. Additionally, MMP-9 expression was demonstrated to serve as a prognostic factor in patients with gastric cancer.
📖 Papers frequently viewed together
11 Citations
7 Authors (Junya Ueda, ..., Hiroshi Yokozaki)
59 Citations
18 Citations
#1Masaya Takehara (Kumamoto University)H-Index: 10
#2Tomoko Nishimura (Kumamoto University)H-Index: 3
Last. Tohru Mizushima (Kumamoto University)H-Index: 55
view all 5 authors...
Alteration in the expression of claudins, consisting of tight junctions (TJs), has been reported in various clinically isolated tumors. Claudins play an important role not only in the intercellular barrier function of TJs but also in migration and invasiveness of cancer cells. However, the use of different types of cells and different claudins in these studies has complicated the picture. In this study, we systematically examined the effect of claudin (claudin-1, -2, -3, -4 and -15) overexpressi...
81 CitationsSource
#1Yong-Lian WuH-Index: 1
#2Sheng ZhangH-Index: 1
Last. Yu-Peng ChenH-Index: 1
view all 4 authors...
AIM: To investigate the relation of expression transformation of claudin-1 with invasiveness and metastasis of gastric carcinoma. METHODS: By using immunohistochemistry, expression of claudin-1 in mucosa and invasive front of 136 gastric adenocarcinoma cases and proliferative index (Ki-67) were detected and analyzed. RESULTS: In mucosa, the claudin-1 over-expression rate of mucinous adenocarcinomas (including signet-ring cell carcinomas) was the highest. It was negatively related with the differ...
28 CitationsSource
Objective: Claudin-2 is an important component of the tight junction (TJ) of epithelial cells, and its protein expression between many tumours is significantly different. It is unclear if Claudin-2 overexpression is a trigger or a consequence during carcinogenesis. The multistage tissues of gastric carcinogenesis provides us a valuable model for determining tumourigenicity. Methods: This paper investigated, for the first time, claudin-2 expression in the pathological paraffin tissues of sinus ve...
17 CitationsSource
#1Takashi Oshima (Yokohama City University Medical Center)H-Index: 29
#2Chikara KunisakiH-Index: 37
Last. Toshio ImadaH-Index: 28
view all 17 authors...
Claudins, members of a large family of adherent junction proteins, regulate the integrity and function of tight junctions and influence tumorigenesis. Studies have suggested that altered levels of different claudins are related to carcinoma-cell invasion and disease progression. This study examined the relationship between the relative expression of claudin genes and clinicopathological factors, especially invasion and metastasis, in patients with colorectal cancer. We studied surgical specimens...
52 CitationsSource
#1Tetsushi Kinugasa (Fukuoka University)H-Index: 19
#2Qun HuoH-Index: 3
Last. Masahide KurokiH-Index: 41
view all 13 authors...
Background: To understand the molecular and morphological alterations in the tight junction in colorectal cancer (CRC) tissues, the expression of eight tight junction proteins in normal and cancer colorectal tissues were compared. Patients and Methods: Adenocarcinoma tissues and paired normal mucosa were resected from surgical specimens of CRC patients. The expression of occludin, ZO-1, ZO-2, and claudin-1 ∼ 5 was analyzed at the mRNA level by quantitative reverse transcription-polymerase chain ...
103 Citations
#1Satoko Morohashi (Hirosaki University)H-Index: 17
#2Tomomi KusumiH-Index: 18
Last. Hiroshi KijimaH-Index: 53
view all 9 authors...
, Claudins (CLDNs) constitute the major transmembrane proteins of tight junctions. It may be hypothesized that changes in or loss of expression of tight junctional proteins such as CLDNs can lead to cellular disorientation and detachment, which is commonly seen in neoplasia. Recent studies have suggested that claudin-1 (CLDN1) plays an important role in invasion and metastasis and claudin-4 (CLDN4) has a particular role in mammary glandular cell differentiation and carcinogenesis. In this study,...
107 CitationsSource
#1Song Xin (SYSU: Sun Yat-sen University)H-Index: 1
#2Chen HuixinH-Index: 1
Last. Chen MinhuH-Index: 1
view all 8 authors...
In this paper, we investigated Cdx2 and claudin-2 expression in pathological paraffin tissues of sinus ventriculi from gastroscopic biopsy to determine the correlation between the expressions of these
25 CitationsSource
#1Junya UedaH-Index: 3
#2Shuho SembaH-Index: 29
Last. Hiroshi YokozakiH-Index: 79
view all 7 authors...
Objective: Claudin-4 plays a key role in constructing the tight junction (TJ), and altered claudin-4 expression has been documented in various human malignancies; however, little is known about the biological significance of claudin-4 in colorectal cancers (CRCs). The aim of this study is to investigate the significance of claudin-4 expression in CRC and its association with clinicopathological factors. Methods: The levels of claudin-4 expression in a total of 129 CRCs and 44 metastatic tumors w...
59 CitationsSource
#1Wen-Ling Kuo (Memorial Hospital of South Bend)H-Index: 1
#2Li-Yu LeeH-Index: 44
Last. Tsann-Long HwangH-Index: 30
view all 9 authors...
Our previous microarray analysis of gastric cancer found that claudin-4 was differentially expressed between intestinal-type gastric cancer (IGC) and diffuse-type gastric cancer (DGC). Claudin-4 is a member of a large family of transmembrane proteins, claudins, essential in the formation and maintenance of tight junctions. To explore the roles of claudin-4 in the two histologically distinct types of gastric cancer, we selected 45 IGC and 48 DGC cases and then analyzed the expression of the prote...
27 CitationsSource
#1Naohisa Oku (Kōchi University)H-Index: 2
#2Eri SasabeH-Index: 13
Last. Tokio OsakiH-Index: 28
view all 5 authors...
Although adherent junctions have been extensively studied, the role of tight junctions in cancer cell invasion is not sufficiently explored. We investigated whether claudin-1, a component of tight junctions, regulated invasion activity in oral squamous cell carcinoma (OSC) cells. The expression of claudin-1, activity of matrix metalloproteinase (MMP)-2, and cleavage of laminin-5 γ2 chains were assessed by Western blot analysis, immunohistochemistry, and zymography in OSC cell lines (OSC-4 and NO...
168 CitationsSource
Cited By24
#1Olga P. Popova (Moscow State University of Medicine and Dentistry)
#2A. V. Kuznetsova (RAS: Russian Academy of Sciences)H-Index: 5
Last. Alexey A. Ivanov (Moscow State University of Medicine and Dentistry)
view all 4 authors...
Claudins are a superfamily of transmembrane proteins, the optimal expression and localization of which are important for the normal physiological function of the epithelium and any imbalance may have pathological consequences. Not only insufficient but also excessive production of claudins in cancer cells, as well as their aberrant localization, equally manifest the formation of a malignant phenotype. Many works are distinguished by contradictory data, which demonstrate the action of the same cl...
OBJECTIVES High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS HPV16E6 infection was detected by polymerase chain reaction. Immunohist...
1 CitationsSource
#1Elham Jafari (KMU: Kerman Medical University)H-Index: 8
#2Somaye Safinejad (KMU: Kerman Medical University)
Last. Ahmad Naghibzadeh-Tahami (KMU: Kerman Medical University)H-Index: 5
view all 4 authors...
Background The relationship between the expressions of matrix metalloproteinases with clinico-pathological data on gastric cancer has been investigated in many countries, but this relationship remains unexplored in Iranian patients. Also, the correlation of the MMPs and the HER-2/neu proto-oncogene with other clinic-pathological variables has been evaluated for several other malignancies, but little effort has been made to shed light on the relationship with gastric cancer. Methods We investigat...
#1Jie Luo (STU: Shantou University)H-Index: 2
#2Huaiming Wang (STU: Shantou University)H-Index: 1
Last. Yi‐Feng Zheng (STU: Shantou University)H-Index: 2
view all 5 authors...
NEW FINDINGS: What is the central question of this study? What is the influence of the interaction between the matrix protein CLDN4 and the PI3K/Akt signalling pathway on tumour progression and chemotherapy sensitivity in gastric cancer? What is the main finding and its importance? Silencing of CLDN4 can promote the growth and proliferation of gastric cancer cells by activating the PI3K/Akt signalling pathway, and thus reduce the sensitivity of gastric cancer cells to chemotherapy. ABSTRACT: Gas...
3 CitationsSource
#1Mohammad Reza Abbaszadegan (MUMS: Mashhad University of Medical Sciences)H-Index: 26
#2Majid Mojarrad (MUMS: Mashhad University of Medical Sciences)H-Index: 12
Last. Meysam Moghbeli (MUMS: Mashhad University of Medical Sciences)H-Index: 15
view all 3 authors...
Gastric cancer (GC) is one of the most common cancers in the world with a high ratio of mortality. Regarding the late diagnosis, there is a high ratio of distant metastasis among GC cases. Despite the recent progresses in therapeutic modalities, there is not still an efficient therapeutic method to increase survival rate of metastatic GC cases. Apart from the various intracellular signaling pathways which are involved in tumor cell migration and metastasis, the local microenvironment is also a c...
1 CitationsSource
#1Hufang Yuan (Hebei Medical University)H-Index: 4
#2Yong Li (Hebei Medical University)H-Index: 8
Last. Zhao-Jie An (Hebei Medical University)H-Index: 1
view all 6 authors...
OBJECTIVE: To explore the inhibitory effect of siRNA-Annexin A7 on growth, migration, and invasion of transplanted gastric cancer in nude mice. METHODS: The siRNA sequence targeting to human Annexin A7 gene was designed, and based on that a pair of complementary oligonucleotides were synthesized, annealed, and cloned into plasmid pGenesil-1.1 to construct recombinant plasmid siRNA-Annexin A7. Transplanted gastric cancer model was established by injecting s.c. nude mice with human gastric cancer ...
3 Citations
#1Fereshte Bibak (Kermanshah University of Medical Sciences)
#2Samane Ahmadi (Kermanshah University of Medical Sciences)
Last. Kheirollah Yari (Kermanshah University of Medical Sciences)H-Index: 12
view all 5 authors...
Context: Gastric carcinoma (GC) is the most commonly diagnosed cancer that has been one of the main causes of cancer death worldwide. The matrix metalloproteinase-2 (MMP2) gene was expressed in the gastric cancer tissues compared to the matched normal tissues that are associated with the metastasis of gastric cancer cells. Objectives: This systematic review was performed to investigate the role of MMP-2 in gastric cancer among the different population. Evidence Acquisition: We searched on electr...
#1Hufang Yuan (Hebei Medical University)H-Index: 4
#2Yong Li (Hebei Medical University)H-Index: 8
Last. Ying-Jie HaoH-Index: 2
view all 11 authors...
High annexin A7 expression is a potential indicator of lymphatic metastasis and poor prognosis in patients with gastric cancer (GC). The mechanism underlying the effects of annexin A7 on GC cells remains unclear. In patients with GC, primary adenocarcinoma tissues had higher annexin A7 expression than adjacent non-cancerous tissues (P < 0.05). Among three human GC cell lines with high, moderate, and low levels of differentiation, respectively, the cell line with the lowest level of differentiati...
5 Citations
#1Julia Baguña Torres (University of Oxford)H-Index: 9
#2James C. Knight (University of Oxford)H-Index: 15
Last. Bart Cornelissen (University of Oxford)H-Index: 23
view all 9 authors...
Purpose Despite its widespread use, the positron emission tomography (PET) radiotracer 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has been shown in clinical settings to be ineffective for improving early diagnosis of pancreatic ductal adenocarcinoma (PDAC). A promising biomarker for PDAC detection is the tight junction protein claudin-4. The purpose of this study was to evaluate a new single-photon emission computed tomography (SPECT) imaging agent, [111In]anti-claudin-4 mAb, with regard to its ...
14 CitationsSource