Biomedical subjects

Albert Roessner

Publications and source records attributed to Albert Roessner.

At least 55 records · Page 3Linked to original sources

PubMed2004

Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are the two entities of chronic inflammatory bowel diseases (IBD). One of the main pathogenic mechanisms is probably a dysregulated immune response triggered by products of the enteric bacterial flora. The goal of this study was to evaluate the effects of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 on inflammatory responses using the DSS-induced experimental colitis model in mice reflecting human IBD. We found that SB203580 improved the clinical score, ameliorates the histological alterations, and reduces the mRNA levels of proinflammatory cytokines. In addition to p38 kinase activity, the "classical" and the "alternative" NF-kappaB pathways were also strongly activated during colitis induction. All three pathways were drastically down-regulated by SB203580 treatment. An analysis of the molecular basis of NF-kappaB activation revealed that Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK), a key component of a pathway leading to NF-kappaB induction, is also strongly inhibited by SB203580. Since RICK is an effector kinase of NOD2, an intracellular receptor of bacterial peptidoglycan, these results support the notion that NOD signaling could play a pivotal role in the IBD pathogenesis. Thus, RICK could represent a novel target for future therapies in human IBD.

Animals↗

PubMed2004

Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia.

BACKGROUND: Evidence is accumulating that several proteases are involved in prostate cancer progression. A locus which is often amplified in prostate cancer is the chromosomal region 20q13. Interestingly, one of the genes encoding the cysteine protease cathepsin X maps to this region. The aim of this study was to assess the expression pattern of cathepsin X in malignant and non-malignant prostatic tissue samples. METHODS: Matched malignant and non-malignant tissue specimens were obtained from 56 men after radical prostatectomy. Cathepsin X was quantified at both protein and mRNA levels using several detection methods: Western blotting, immunohistochemistry, quantitative RT-PCR, and in situ hybridization. Furthermore, genomic DNA was analyzed by PCR for possible gene amplification. RESULTS: Immunohistochemical analysis of formalin-fixed, paraffin-embedded sections of radical prostatectomy specimens was performed utilizing a polyclonal antibody against human procathepsin X and revealed staining of acinar basal cells in normal prostate glands. Prostatic intraepithelial neoplasias (PINs) and prostate carcinomas stained highly positive for cathepsin X, showing a significant difference to the staining of normal prostate glands. In contrast, relatively weak and heterogeneous staining was observed for cathepsins F, B, and L. Up-regulation of cathepsin X at the protein level was confirmed by Western blotting. No statistically significant difference was observed at the mRNA level. PCR of genomic DNA revealed that cathepsin X up-regulation most likely occurs in the absence of genomic amplification. CONCLUSIONS: The high expression levels of cathepsin X both in PIN and invasive adenocarcinomas of the prostate suggest that cathepsin X may play a role in the early tumorigenesis of prostate cancer. Further studies are needed to define the utility of this cysteine protease as a diagnostic marker for the early detection of prostate cancer.

Aged↗

PubMed2004

INK4a-ARF alterations in Barrett's epithelium, intraepithelial neoplasia and Barrett's adenocarcinoma.

INTRODUCTION: The INK4a-ARF [CDKN2A]- locus on chromosome 9p21 encodes for two tumour suppressor proteins, p16INK4a and p14ARF, which act as upstream regulators of the Rb-CDK4 and p53 pathways. To study the contribution of each pathway to the carcinogenesis of Barrett's adenocarcinoma, we analysed the alterations of p14ARF and p16INK4a in preneoplastic and neoplastic lesions of this disease. MATERIALS AND METHODS: After microdissection, DNA of 15 Barrett's adenocarcinomas, 40 Barrett's intraepithelial neoplasms (n=20 low- and n=20 high-grade) and 15 Barrett's mucosa without neoplasia was analysed for INK4-ARF inactivation using DNA sequence and loss of heterozygosity (LOH) analysis, methylation-specific polymerase chain reaction, restriction-enzyme-related polymerase chain reaction and immunohistochemistry. RESULTS: We detected 9p21 LOH, p16INK4a methylation and p16INK4a mutations in Barrett's adenocarcinomas in 5 of 15 (33%), 8 of 15 (53%) and 1 of 15 (7%) patients, respectively. P14ARF was methylated in 3 of 15 (20%) adenocarcinomas. In Barrett's intraepithelial neoplasia, p16INK4a was altered in 12 of 20 (60%) high-grade and in 4 of 20 (20%) low-grade intraepithelial neoplasms. In Barrett's mucosa without intraepithelial neoplasia p16(INK4a) was methylated in one case (7%). P14ARF was intact in Barrett's mucosa without intraepithelial neoplasia. CONCLUSIONS: We conclude that most Barrett's intraepithelial neoplasms contain genetic and/or epigenetic INK4a-ARF alterations. Methylation of p16INK4a appears to be the most frequent epigenetic defect in the neoplastic progression of Barrett's tumourigenesis.

Barrett Esophagus↗

PubMed2004

A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal human gastric mucosa.

TFF3 is a member of the trefoil factor family (TFF) peptides, which enhance the surface integrity of mucous epithelia, and is typically secreted by intestinal goblet cells together with the mucin MUC2. Reports of the expression of TFF3 within the normal human stomach are contradictory and the precise localisation of TFF3 is unknown. We have mapped the human gastric mucosa by reverse transcription/polymerase chain reaction and Western blot analysis and by immunohistochemistry. Small amounts of TFF3 were detectable in the oxyntic mucosa of the corpus, whereas TFF3 synthesis increased sharply distal to the corpus-antrum transitional zone. TFF3 secretion was demonstrated in the antrum, the pyloric region and the proximal duodenum. High TFF1 levels were present in all regions of the gastric mucosa including the corpus, whereas the proximal duodenum was nearly devoid of TFF1. Immunohistochemistry localised TFF3 to antral and pyloric surface mucous cells. In the antrum, an increasing concentration gradient was found towards cells deeper in the isthmus. TFF1 was confined to superficial pit cells in the antrum. TFF3 was also present in specific layers of the laminated mucous gel of the antral and pyloric regions and variable concentrations of TFF3 (2-62 nmol/l) were measured in gastric juice. Here, a probably N-terminally shortened variant is present that forms disulphide-linked dimers. Thus, TFF3 is a typical secretory peptide of the normal human antral and pyloric gastric mucosa and has a gastric expression pattern different from that of TFF1 and TFF2. TFF3 might therefore have important physiological functions in the stomach, e.g. as a luminal surveillance peptide maintaining particularly the integrity of the antral and pyloric mucosa.

Gastric Juice↗

PubMed2004

Metachronous and multiple aneurysmal bone cysts: a rare variant of primary aneurysmal bone cysts.

In 1942, Jaffe and Lichtenstein introduced the term aneurysmal bone cyst (ABC). Primary ABC is characterized by the presence of spongy or multi-cameral cystic tissue filled with blood. The process is benign, but it is locally destructive and has a high propensity for recurrence. In this paper, we present the third case of multiple metachronous primary ABCs as a rare variant of ABC. We describe the 10-year history of a 12-year-old boy with metachronous multiple primary ABCs at five different sites (right proximal humerus, right ulna, bilateral distal radius and right lateral clavicle). Furthermore, our patient suffered from vascular malformations, such as aortic isthmus stenosis, hypoplastic thoraco-abdominal aorta and bilateral renal artery stenosis. To date, in contrast to solitary ABC, the multiple lesions have been found more frequently in male individuals. Using interphase cytogenetics, we analyzed three of five of the patient's ABCs and one of these was also analyzed by GTG-banding. No chromosomal abnormalities were found. Significantly, we excluded the missense mutation of codon 201 in guanine nucleotide-binding protein 1 gene consistently found in McCune-Albright syndrome (MAS) and in non-MAS cases of polyostotic fibrous dysplasia of bone with or without secondary ABC.

Blood Vessels↗

PubMed2004

Cleavage of AL amyloid proteins and AL amyloid deposits by cathepsins B, K, and L.

Cathepsin (Cath) B, CathK and CathL are cysteine proteases that participate in the lysosomal protein degradation system and are expressed in macrophages, epithelioid cells, and multinucleated histiocytic giant cells (MGCs). Both macrophages and MGCs are commonly found adjacent to immunoglobulin light chain-associated (AL) amyloid deposits, which raised the question of whether cysteine proteases are able to cleave AL amyloid proteins and AL amyloid deposits. The present study has investigated whether recombinant human CathB, CathK, and CathL are able to degrade AL(VlambdaVI) amyloid proteins and AL amyloid deposits. Using immunohistochemistry, CathB, CathK, and CathL were found adjacent to AL amyloid deposits. In vitro degradation experiments using purified AL amyloid proteins showed that CathB, CathK, and CathL degrade AL(VlambdaVI) amyloid proteins. Furthermore, using unfixed tissue sections from an amyloidotic spleen as an in vitro model for extracellular proteolysis of intact amyloid deposits, it was demonstrated that all three cysteine proteases are also capable of degrading AL amyloid in situ. This is the first study to show that cysteine proteases are able to cleave AL amyloid proteins. However, the efficiency with which proteolysis occurs depends on the concentration of active protease recruited at the sites of amyloid deposition, and possibly on the structure of the AL amyloid proteins.

Aged↗

PubMed2004

MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC).

The prognostic impact of MDM2 amplification in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the occurrence of MDM2 amplification in surgically treated NSCLC patients. Molecular data were correlated with clinicopathological factors and evaluated for their prognostic value. The study group included 116 NSCLC patients who underwent pulmonary resection between 1996 and 1999. MDM2 amplification was assessed by real-time PCR using hybridization probe format on a LightCycler (Roche). The calculated ratio was a MDM2 value normalized to the amplification of the housekeeping gene phenylalaninhydroxylase (PAH). Survival curves were drawn according to the Kaplan-Meier method and compared with the use of the log-rank test. Multivariate analysis was based on Cox regression analysis. MDM2 amplification was found in 24 patients (21%). There was no relationship between MDM2 amplification and clinicopathological factors, such as sex, age and stage of disease, pT, pN, histology and tumor differentiation. Median disease-free survival (DFS) in patients with and without MDM2 amplification was 3 and 31 months, and 5-year DFS 24 and 33%, respectively (log-rank, P = 0.02). Likewise, median overall survival (OS) in patients with and without MDM2 amplification was 9 and 33 months, respectively, and 5-year OS 24 and 39%, respectively (log-rank, P = 0.01). The strong prognostic relevance of MDM2 amplification for both DFS and OS was confirmed in multivariate analysis (P < 0.01 for both comparisons). Our results suggest that MDM2 gene amplification analysis provides additional prognostic information in surgically treated NSCLC patients.

Adenocarcinoma↗

PubMed2004

TFF3 expression at the esophagogastric junction is increased in gastro-esophageal reflux disease (GERD).

At the gastric cardia, the molecular mechanisms of inflammation and metaplasia are incompletely understood. Thus, the aim of this study was to determine the expression of TFF1, TFF2 and TFF3 at this site and correlate these data with Helicobacter pylori infection or gastro-esophageal reflux disease (GERD). In 27 patients without intestinal metaplasia at the cardia, endoscopic biopsies were obtained for histology and RT-PCR. TFF1 and TFF2 were expressed in all cardia samples. TFF3 expression was significantly more frequent at the cardia (n = 15/24) than in the corpus (n = 2/26). TFF3 expression at the cardia was mainly observed in GERD patients, and there was a clear tendency towards higher interleukin-8 (IL-8) transcription levels; whereas TFF3 expression was not correlated with the H. pylori status or to tumor necrosis factor-alpha (TNF-alpha) expression. The expression of TFF3 at the cardia may represent an adaptation to GERD and precede the development of Barrett's esophagus.

Barrett Esophagus↗

PubMed2004

Epithelial cell preparation for proteomic and transcriptomic analysis in human pancreatic tissue.

Standardized sample preparation procedures constitute a prerequisite for obtaining reliable and reproducible results in gene expression research in humans. In particular, in diseases such as pancreatic cancer and pancreatitis, isolating epithelial cells is an important step preceding such research. In pancreatic tissue, the high amount of RNAases is a further problem when it comes to obtaining high-quality RNA, and the presence of secreted proteases accelerates protein degradation. We developed a successful method that addresses these different problems. This method, which uses epithelial cell surface antibody Ber-Ep4, proteases, and RNAases inhibitors, leads to a significant enrichment (> 95% purity) of epithelial cells from fresh human tissue samples and allows for both proteomics (Western Blot, 2D PAGE) and transcriptomics studies (rtPCR, cDNA microarray). Compared with other cell purification procedures, this method is characterized by several advantages: a large quantity of cells available for downstream analysis, combined transcriptomics and proteomics studies using the same samples, better reproducibility of proteomics studies, and an acceptable yield (63%) for gene expression arrays studies. Moreover, a quality control protocol addressing the needs of the industry and the requirements of regulatory agencies is proposed.

Epithelial Cells↗

PubMed2004

Proteomics in pathology, research and practice.

Using more reliable and sophisticated protein biochemical techniques, it is possible to perform large scale, partly high-throughput characterization of the human proteome. Two-dimensional electrophoresis (2-DE) and mass spectrometry largely contribute to the identification of proteins and peptides. 2-DE has been used to study differential expression of peptides and proteins in various disease entities, searching for new diagnostic and therapeutic targets. However, 2-DE usually requires large amounts of starting material, is time-consuming, and reveals only a fraction of the proteins present in a given sample. More recently, the ProteinChip technology coupled with bioinformatics has gained considerable attention. This technique uses surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF/MS) to screen any protein source for putative disease biomarkers in a spectrum from 2 to 20 kDa. Between 15,500 (low resolution SELDI TOF) and > 400,000 peptides and proteins (high-resolution SELDI-TOF) can be resolved from a small sample volume (microl-range). Several studies have provided evidence that ProteinChip technology is capable of detecting early stage cancer by its unique cancer-specific proteomic finger prints, with sensitivities and specificities reaching far beyond well established serum-based tumor markers. In this review, we summarize the recent developments of proteomics in research and pathology, and critically discuss putative limitations and future applications of disease-specific biomarkers. Special emphasis is put on the former Human Protein Index project.

Biomedical Research↗

PubMed2004

Retention of the arginine allele in codon 72 of the p53 gene correlates with poor apoptosis in head and neck cancer.

The allele constitution at codon 72 of the p53 gene (CGC-arginine or CCC-proline) plays a major role in inducing apoptosis in p53 mutant cells. To verify this, we determined GC-status, p53-mutations, and p53-loss of heterozygosity (LOH) in a group of 54 squamous cell carcinomas of the head and neck (SCCHN). A novel approach, using a one-step real-time PCR analysis with fluorescent hybridization probes, was applied to detect the GC status in tumors and corresponding blood samples. p53 mutations in exons 4 to 8 were detected by PCR-SSCP-sequencing analysis. Apoptosis was determined immunohistochemically using antibodies against Fas, FasL, p53, Bcl2, and terminal deoxy-transferase-mediated dUTP nick end labeling (TUNEL) staining. The overall frequency of p53-LOH in SCCHN was 45.2%. In cases of LOH, there was a preferential loss of the proline allele, which was associated with an up-regulation of Bcl2 and lack of co-expression of Fas/FasL and, thus, impaired apoptosis (P < 0.001). Apoptosis was not observed in tumors carrying the arginine allele. p53 mutations were detected in 29.6% of SCCHN and preferentially occurred at the arginine allele (P = 0.01). p53 alterations were more frequently observed in tumors of the oral cavity, oropharynx and hypopharynx, whereas they were rare in larynx carcinomas (P = 0.07). The p53-LOH status was not found to be significantly correlated with sex, age, TNM-status, or tumor grading. We conclude that apoptosis is correlated with the allelic status of codon 72 in SCCHN. Homozygous proline 72 appears to be an important regulator of apoptosis via the Fas/FasL pathway in SCCHN.

Adult↗

PubMed2004

Angiotensin I-converting enzyme (CD143) is down-regulated in focal nodular hyperplasia of the liver.

In surgical pathology, focal nodular hyperplasia (FNH) is sometimes difficult to diagnose, and liver cirrhosis (LC) and hepatocellular adenoma (HA) are often among the differential diagnoses. Recently, we found a reduced expression of angiotensin I-converting enzyme (CD143) in FNH compared with cirrhotic and noncirrhotic liver. Intrigued by this observation, we investigated the expression pattern of CD143 in FNH, LC, and HA and its possible diagnostic value. The expression of CD143 was studied by immunohistochemistry in 20 FNHs, 13 corresponding extralesional noncirrhotic liver parenchyma, 20 patients with LC, and four HAs. Endothelial cells were identified with antibodies directed against CD31 and CD34. CD31+, CD34+, and CD143+ sinusoidal endothelial cells were found in extralesional liver, LC, HA, and FNH. However, the number of CD143+ sinusoidal endothelial cells and the intensity of immunostaining were significantly reduced in FNH compared with extralesional liver, LC, and HA. The expression of CD143 was further assessed using a numerical scoring system ranging from 0 to 6. The mean immunoreactivity score for CD143 was 2.4 +/- 1.7 for sinusoidal endothelial cells in FNH, 5.7 +/- 0.6 in extralesional liver, 4.8 +/- 1.1 in LC, and 5.8 +/- 0.5 in HA. The differences between the mean immunoreactivity scores for CD143 were highly significant. The difference between FNH and extralesional liver was confirmed on transcriptional level by fluorescence-mediated real-time RT-PCR, which also showed a significantly decreased level of CD143 mRNA in FNH. Our study provides evidence that CD143 is down-regulated in FNHs and that the phenotype of endothelial cells lining the sinusoids in FNH differs from those in non-neoplastic liver, LC, and HA. The observed variations in expression patterns for CD143 might be of diagnostic use in surgical pathology.

Adenoma, Liver Cell↗

PubMed2004

Helicobacter pylori-mediated gastritis induces local downregulation of secretory leukocyte protease inhibitor in the antrum.

Helicobacter pylori-infected subjects exhibited a strong decline in antral secretory leukocyte protease inhibitor (SLPI) levels compared to H. pylori-negative subjects and subjects from whom H. pylori had been eradicated (P = 0.002). This reduction was specific for the antrum, whereas SLPI expression in corpus and duodenum was not affected. Antral SLPI levels were inversely correlated with inflammatory scores of antrum-predominant gastritis.

Adult↗

PubMed2004

Expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, cathepsin B, and urokinase plasminogen activator in non-skull base chordoma.

We analyzed the expression of proteases and the clinicopathologic significance in non-skull base chordoma (NSBC). By using immunohistochemical techniques, we studied the expression of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, cathepsin B (CatB), and urokinase plasminogen activator (uPA) in 29 NSBCs and compared these data with clinicopathologic parameters and the expression of cell differentiation markers. Expression of MMP-1 (P = .092), MMP-2 (P = .041), and CatB (P = .058) was associated with nuclear pleomorphism, a previously described adverse prognostic indicator. Expression of cytokeratin 8 correlated with that of MMP-1 (P = .005), MMP-2 (P = .002), and uPA (P = .032). Patients with higher MMP-2 expression had a poorer prognosis than those with lower MMP-2 expression (P = .013). We believe that NSBCs with nuclear pleomorphism or stronger epithelial character have a higher invasive ability than those without. In addition, high MMP-2 expression was an indicator of an unfavorable clinical outcome in NSBC.

Adult↗

PubMed2004

Cathepsins K, L, B, X and W are differentially expressed in normal and chronically inflamed gastric mucosa.

The expression of cathepsins K, L, B, X and W was studied by quantitative RT-PCR in normal and inflamed gastric mucosa (antrum, corpus, cardia). Cathepsins B, L, K and X were expressed ubiquitously. In contrast, cathepsin W was expressed at very low levels. Infection by Helicobacter pylori caused a significant induction of cathepsin X (p<0.008), whereas the other cathepsins were not or only locally affected by H. pylori infection or reflux disease. Immunohistochemistry revealed specific expression of cathepsin X (macrophages), cathepsin K (parietal cells) and cathepsin W (lymphocytes), whereas cathepsins B and L were predominantly expressed in epithelial cells.

Cathepsin B↗

PubMed2004

Ectopeptidases are differentially expressed in hepatocellular carcinomas.

We investigated the expression pattern of neprilysin (CD10), aminopeptidase N (CD13) and angiotensin-I converting enzyme (CD143) in hepatocellular carcinomas (HCC), and their putative roles in hepatocarcinogenesis. Tissue samples were obtained from 31 patients with HCC. Tissue samples obtained from non-neoplastic liver, fetal livers and focal nodular hyperplasias (FNH) were used by comparison. Transcription and expression of CD10, CD13, and CD143 were studied by quantitative RT-PCR, Western blotting, and immunohistochemistry. Cell proliferation assays were performed with the C3A hepatoma cell line. The mRNA and protein of each of CD10, CD13 and CD143 were differentially expressed in HCCs. CD10 was decreased in HCCs as compared to non-neoplastic liver tissue, while CD13 and CD143 were mildly increased. In fetal liver and FNHs, the expression of CD10 was less intense than in the surrounding non-tumorous liver. The expression patterns of CD13 and CD143 in fetal livers and FNHs were similar to HCCs and were predominantly localized in bile canaliculi (CD13) and endothelial cells (CD143). CD10 and CD13 mRNAs were expressed by C3A cells and blocking either CD10 or CD13 ectopeptidase activity retarded cell growth significantly in vitro. We demonstrate that ectopeptidases are differentially expressed in HCCs and may have influence on tumor biology. Overall, expression of CD10 in non-neoplastic and neoplastic hepatocytes appears to correlate inversely with their state of proliferation or differentiation. CD13 shows a characteristic canalicular distribution pattern and may be important for cell polarization and bile compartmentalization in HCCs, while CD143 may influence angiogenesis.

Adult↗

PubMed2004

Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism.

For centuries, the black seed (Nigella sativa) herb and oil have been used in Asia, Middle East and Africa to promote health and fight disease. Thymoquinone (TQ), the most abundant constituent present in black seed, is a promising dietary chemopreventive agent. We investigated the effects of thymoquinone (TQ) against HCT-116 human colon cancer cells and attempted to identify its potential molecular mechanisms of action. We report that TQ inhibits the growth of colon cancer cells which was correlated with G1 phase arrest of the cell cycle. Furthermore, TUNEL staining and flow cytometry analysis indicate that TQ triggers apoptosis in a dose- and time-dependent manner. Apoptosis induction by TQ was associated with a 2.5-4.5-fold increase in mRNA expression of p53 and the downstream p53 target gene, p21WAF1. Simultaneously, we found a marked increase in p53 and p21WAF1 protein levels but a significant inhibition of anti-apoptotic Bcl-2 protein. Co-incubation with pifithrin-alpha (PFT-alpha), a specific inhibitor of p53, restored Bcl-2, p53 and p21WAF1 levels to the untreated control and suppressed TQ-induced cell cycle arrest and apoptosis. p53-null HCT-116 cells were less sensitive to TQ-induced growth arrest and apoptosis. These results indicate that TQ is antineoplastic and pro-apoptotic against colon cancer cell line HCT116. The apoptotic effects of TQ are modulated by Bcl-2 protein and are linked to and dependent on p53. Our data support the potential for using the agent TQ for the treatment of colon cancer.

Apoptosis↗

PubMed2004

The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer.

Due to their extracellular orientation, the ectopeptidases CD10, CD13, CD26, and CD143 have numerous functions, including the post-secretory processing of the neuropeptides and peptide hormones involved in the regulation of growth and differentiation in the gastrointestinal tract. We investigated the transcription and expression pattern of these four ectopeptidases in gastric carcinomas (GC), the corresponding non-neoplastic epithelium, a selection of lymph node metastases (LNM), and the MKN28, AGS, NCI-N87, KATO III gastric cancer cell lines. The gastric foveolar epithelium did not express CD10, CD13, or CD143, but the intestinal metaplasia demonstrated strong immunoreactivity at the brush border for all four ectopeptidases. CD10, CD13, and CD143 were significantly up-regulated in GCs and the lymph node metastases, confirming that they are important for the tumor cell biology. However, there is a lack of correlation between expression in intestinal metaplasia and tumor, as well as in tumor and LNM. Cell proliferation assays were performed with MKN28 and AGS, in which inhibition of CD10 significantly reduced the growth of both cell lines, and inhibition of CD13 significantly increased the proliferation of the AGS cells, indicating that the ability to degrade gastrointestinal peptides may play an important role in the pathobiology of gastric cancer.

Adult↗