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Biomedical subjects

Wataru Yasui

Publications and source records attributed to Wataru Yasui.

At least 73 records · Page 4Linked to original sources
PubMed2003

Rapid and preferential induction of ATF3 transcription in response to low doses of UVA light.

Long-wavelength UV light (UVA) is known to induce transcription of various genes in the cell and to cause a variety of pathological or protective responses in the skin. To find additional UVA-responsive genes, human skin-derived fibroblasts were exposed to UVA under non- or partially lethal conditions, and the effects of UVA on the transcriptional profile were examined by using DNA microarray and RT-PCR. Transcription of several genes including those already known to be UVA-responsive was induced to a significant extent under 50% lethal conditions of exposure. Among those, ATF3 was the most sensitive and its transcription was increased 10-fold within 1h. Even at a non-lethal dose of UVA (8J/cm(2)), it was increased 8-fold, if cells were cultured for 3h post-exposure. Typical immediate-early genes such as c-fos and c-jun were not affected at this dose. We thus suggest that ATF3 could be a key regulator for a variety of cellular responses in the skin, particularly to low doses of UVA.

Base Sequence↗
PubMed2003

The promoter methylation status of the DNA repair gene O6-methylguanine-DNA methyltransferase in ulcerative colitis.

Patients with long-standing and extensive ulcerative colitis (UC) have an increased incidence of colorectal cancer (CRC). It has been reported that a DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT) is inactivated by promoter hypermethylation in sporadic CRCs. Hence, we investigated the promoter methylation status of MGMT by methylation specific polymerase chain reaction (PCR) in a total of 67 tissue samples (61 non-cancerous tissues and 6 cancer tissues) from 24 patients with UC. Promoter hypermethylation of MGMT was detected in one well-differentiated adenocarcinoma (16.7%) of 6 cancer samples and not detected in any of adenomas and dysplasias. In non-dysplastic tissues, promoter hypermethylation of MGMT was detected in 2 (3.7%, mucosa with mild inflammation) of 54 samples. The frequency of MGMT promoter hypermethylation in UC-associated CRCs found in this study (16.7%) is obviously lower than previously reported in sporadic CRCs (39.0-42.0%). We also confirmed that 42.9% (6/14) of sporadic CRCs showed the promoter methylation. These findings indicated that promoter hypermethylation of the MGMT gene is infrequent in patients with UC, and may not closely contribute to UC-associated colorectal tumorigenesis. A different genetic pathway for tumor progression may exist between sporadic CRC and UC-associated CRC.

Adult↗
PubMed2003

Hypoxia-inducible factor-1alpha polymorphisms associated with enhanced transactivation capacity, implying clinical significance.

Hypoxia-inducible factor-1 (HIF-1) is a pivotal factor that regulates cellular responses to hypoxia and is presumably linked to regulation of angiogenesis and tumor growth. We assessed the difference in transcription activity of two HIF-1alpha polymorphic variants (P582S and A588T), along with molecular epidemiological study among head and neck squamous cell carcinoma (HNSCC) patients. Both HIF-1alpha variants revealed significantly higher transcription activity than wild-type (WT) did, under normoxic and hypoxic conditions (P < 0.02). Furthermore, tumors from HNSCC patients with heterozygous alleles having P582S or A588T had significantly increased numbers of microvessels compared with those with homozygous WT (P = 0.02). In addition, all patients with tumors of T1 (below 2 cm diameter) were WT, while 14 of 47 patients with tumors of > or =T2 were heterozygous. The elevated transactivation capacity of variant forms of HIF-1alpha implies a role of HIF-1alpha polymorphisms in generating individually different tumor progression.

Amino Acid Sequence↗
PubMed2003

Expression of osteoprotegerin correlates with aggressiveness and poor prognosis of gastric carcinoma.

Osteoprotegerin (OPG), identical with osteoclastogenesis inhibitory factor, is a member of a subgroup of the tumor necrosis factor (TNF)-receptor superfamily, which functions as a soluble decoy receptor. It has been reported that OPG expression is associated with bone metastasis of cancer of the breast and prostate. In the present study, we examined the expression of OPG in gastric carcinomas using immunohistochemistry and reverse-transcription polymerase chain reaction methods, and compared with clinicopathological parameters. The expression of OPG mRNA was confirmed in a gastric carcinoma cell line (MKN-7) and gastric carcinoma tissues. Immunohistochemically, strongly positive staining of OPG was found in 65% (67/103) of gastric carcinomas, whereas OPG protein was not detected in non-neoplastic mucosal epithelia. The expression of OPG protein in gastric carcinoma tissues correlates significantly with depth of tumor invasion, nodal metastases and advanced tumor stage. Furthermore, the prognosis of the cases with strong OPG expression was significantly worse than those with weak or no expression of OPG. These results suggest that OPG may participate in stomach carcinogenesis, invasion and metastasis, and may serve as a novel molecular marker for aggressive gastric cancer.

Adenocarcinoma↗
PubMed2003

Expression of thrombospondin-1 is correlated with microvessel density in gastric carcinoma.

Thrombospondin-1 (TSP-1) has been shown to play a role in angiogenesis in a variety of cancers, but some studies indicated a difference in the mechanism of TSP-1 on neovascularization according to organ or histological type. Wild-type p53 protein has been shown to induce TSP-1 expression. We examined the expression of TSP-1 protein in 80 gastric carcinomas using immunohistochemistry and studied the relationship with microvessel counts, p53 expression and clinicopathological factors. We also performed reverse-transcriptase polymerase chain reaction analysis for the TSP-1 mRNA expression in gastric carcinoma cell lines and gastric cancer tissue after laser capture microdissection. Strong expression of TSP-1 protein was detected in 30 (38%) of the 80 cases. Positive staining for TSP-1 was seen in the cytoplasm of the cancer cells. TSP-1 mRNA expression was confirmed in a majority of gastric carcinoma cell lines and carcinoma tissues. Microvessel counts were significantly higher in tumors with strong TSP-1 protein expression than in those without expression or weak expression of TSP-1 ( P=0.011). No significant correlation was found between TSP-1 expression and p53 staining and clinicopathological factors. Our results support an idea that increased TSP-1 expression may be associated with an angiogenic phenotype in gastric carcinoma and suggest that TSP-1 may play diverse roles in each organ.

Adenocarcinoma↗
PubMed2003

A possible role for the loss of CD27-CD70 interaction in myelomagenesis.

CD27 is a marker of memory B cells and its interaction with its ligand, CD70, is very important for differentiation into plasma cells. Although CD27 is detected on normal plasma cells, its expression is significantly reduced with the progression of multiple myeloma (MM), including monoclonal gammopathy of undetermined significance (MGUS). CD27+ myeloma cells are thought to represent an early phase of myeloma, as CD27+ plasma cells from MM patients were found to be composed of normal plasma cells (CD19+/CD38++) and myeloma cells (CD19-/CD38++), and monoclonality was detected in the CD27+/CD38++ fraction. Given that the lack of CD27 on plasma cells is related to myelomagenesis and that the pro-apoptotic protein Siva is thought to bind to the cytoplasmic tail of CD27, we analysed alterations of cell growth and genes caused by co-culturing CD27-transfected myeloma cell lines (U266, KMS-5) with CD70-transfected NIH3T3 cells. CD27-CD70 interaction could not induce apoptosis in either type of myeloma transfectant, and binding between Siva and CD27 was not detected. cDNA microarray (human apoptosis CHIP) analysis showed a significant upregulation of expression of the ectodermal neural cortex 1 (ENC1) gene by CD27-CD70 interaction compared with CD27 transfection alone. These findings show that the relationship between the loss of CD27 and oncogenesis of plasma cells is not simple. It remains unclear whether the lack of CD27 leads to evasion of apoptosis.

3T3 Cells↗
PubMed2003

Small cell carcinoma of the extrahepatic bile duct: case report and immunohistochemical analysis.

A small cell carcinoma of the extrahepatic bile duct in a 75-year-old Japanese man is reported. The patient suffered from obstructive jaundice, and percutaneous transhepatic cholangiography-drainage (PTCD) revealed a massive lesion in the lower common bile duct. Because it was diagnosed as a malignant tumor, pancreaticoduodenectomy was performed. A nodular infiltrating tumor measuring 4.5 x 3.0 x 2.0 cm was located in the intrapancreatic portion of the extrahepatic bile duct. Histologically, the tumor was composed of a dense proliferation of small atypical cells with a little region of high-grade dysplasia in the adjacent epithelium of the common bile duct. Tumor cells were immunoreactive to neuroendocrine markers such as chromogranin A, synaptophysin, CD56, and Leu7. Although carcinoma cells invaded into pancreas and duodenum, there were no histological findings that indicated the carcinoma arose from the mucosa of either the pancreatic duct or duodenum. These results indicated that the tumor was a small cell carcinoma derived from the epithelium of the extrahepatic bile duct; a rare neoplasm with only a few cases reported. A few neuroendocrine cells were recognized in the adjacent epithelium of the extrahepatic bile duct, suggesting that the tumor cells might be derived from them. Using immunohistochemical examination, no p53 abnormality was found. Tumor cells showed positive nuclear staining for p16, while negative for cyclin D1, suggesting that functional retinoblastoma protein (pRB) might be lost in the p16/pRB pathway, as in small cell lung cancer.

Aged↗
PubMed2003

DNA methylation of multiple genes in gastric carcinoma: association with histological type and CpG island methylator phenotype.

Hypermethylation of CpG islands is associated with silencing of various tumor suppressor genes. Recent studies on colorectal and gastric cancer have identified a CpG island methylator phenotype (CIMP), which involves the targeting of multiple genes by promoter hypermethylation. For determination of association between DNA methylation pattern or histological type and CIMP status in gastric carcinoma, CpG islands in the promoters of hMLH1 and CDH1 genes, CpG islands overlapping exon 1 of MGMT and p16(INK4a) genes, and a non-CpG island in exon 1 of the RAR-beta gene were studied. The presence of the CIMP was determined by monitoring five methylated in tumor (MINT ) loci in 103 gastric carcinomas. Among the 103 gastric carcinomas, DNA hypermethylation was detected in the following frequencies: 14 (14%) for hMLH1, 26 (25%) for MGMT, 26 (25%) for p16(INK4a), 54 (52%) for CDH1, and 53 (52%) for RAR-beta. Forty-two (41%) of 103 gastric carcinomas were positive for the CIMP. CIMP and hypermethylation of p16(INK4a) gene were found more frequently in intestinal and diffuse-adherent types than in diffuse-scattered type (P = 0.013 and 0.017, respectively). In contrast, hypermethylation of the CDH1 and RAR-beta genes was more common in the diffuse-scattered type than in the other types (P = 0.008 and 0.007, respectively). In intestinal- and diffuse-adherent-type gastric carcinomas, we found significant associations between the presence of the CIMP and hypermethylation of several genes: hMLH1 (P = 0.006), p16(INK4a) (P = 0.018), CDH1 (P = 0.024), and RAR-beta (P = 0.044). Our overall results suggest that in some intestinal- and diffuse-adherent-type gastric carcinomas, DNA hypermethylation affects non-specific gene promoters concordantly, at least in part, whereas in diffuse-scattered-type gastric carcinoma, DNA hypermethylation affects specific genes such as CDH1 and RAR-beta.

CpG Islands↗
PubMed2003

DNA hypermethylation and histone hypoacetylation of the HLTF gene are associated with reduced expression in gastric carcinoma.

The SWI/SNF proteins are ATP-dependent chromatin remodeling enzymes that have been implicated in the regulation of gene expression. Recent studies have shown that members of the SWI/SNF superfamily can function as tumor suppressor genes. DNA methylation and transcriptional inactivation of the HLTF gene, which is a homologue to the SWI/SNF genes, have been observed in colon cancer. In the present study, we studied the DNA methylation status of the HLTF gene by methylation-specific PCR in 50 gastric carcinoma tissues, and seven gastric carcinoma cell lines and compared the methylation status with the levels of HLTF mRNA expression. DNA methylation of the HLTF gene was found in 25 (50%) of 50 gastric carcinomas, and levels of HLTF mRNA were associated with methylation status of HLTF (P = 0.027; Mann-Whitney U test). No correlations were found between HLTF mRNA levels and DNA methylation and T grade, N grade, tumor stage, or histological type. In corresponding non-neoplastic mucosae, DNA methylation of the HLTF gene was found in 1 (7%) of 15 samples. The methylated allele was not detected in any of 10 normal gastric mucosae from 10 healthy volunteers. Among seven gastric carcinoma cell lines, the KATO-III cell line showed loss of HLTF mRNA expression associated with DNA methylation. This loss was rectified by treatment with both Aza-2'-deoxycytidine, a demethylating agent, and trichostatin A, a histone deacetylase inhibitor. Chromatin immunoprecipitation assay revealed that the acetylation levels of histones H3 and H4 in the 5' CpG island of the HLTF gene were inversely associated with DNA methylation status. These results suggest that transcriptional inactivation of HLTF by aberrant DNA methylation and histone deacetylation may be involved in stomach carcinogenesis through down-regulation of HLTF expression.

Acetylation↗
PubMed2003

Histone acetylation and gastrointestinal carcinogenesis.

The importance of altered histone acetylation in gastrointestinal carcinogenesis, especially in relation to invasion and metastasis, is described. Histone acetylation and chromatin remodeling linked with CpG island methylation play a major role in epigenetic regulation of gene expression. Acetylation of histones through an imbalance of histone acetyltransferases and deacetylases disrupts nucleosome structure, which leads to DNA relaxation and subsequent increase in accessibility to transcription factors. The expression of acetylated histone H4 is reduced in a majority of gastric and colorectal cancers, indicating the low level of global histone acetylation in tumor cells. Moreover, reduced histone acetylation is significantly associated with depth of tumor invasion and nodal metastasis of gastrointestinal cancers. A histone deacetylase inhibitor, trichostatin A (TSA), induces growth arrest and apoptosis and suppresses invasion of cancer cells. Treatment with TSA, which is followed by increased histone acetylation in the promoters, induces the expression of many genes that are suppressors of invasion and metastasis, including tissue inhibitors of metalloproteinase and nm23H1/H2, in addition to negative cell cycle regulators and apoptosis-related molecules. Our approach, serial analysis of gene expression (SAGE), enabled us to identify a gene that is a novel candidate for a metastasis suppressor, whose expression is induced by histone acetylation. These findings suggest that, by modifying gene expression, histone deacetylation may participate not only in tumorigenesis but also in invasion and metastasis. Therefore, histone acetylation should be a promising target for cancer therapy, especially against invasive and metastatic disease, but also for cancer prevention.

Acetylation↗
PubMed2003

Reduced expression of the TSP1 gene and its association with promoter hypermethylation in gastric carcinoma.

Thrombospondin-1 (TSP1) is a potent peptide shown in some tumor systems to be linked with angiogenesis. Epigenetic alteration of TSP1 has been reported in various primary tumors. However, the expression pattern of TSP1 has not been characterized in gastric carcinoma. We measured levels of TSP1 mRNA expression using quantitative RT-PCR in 30 gastric carcinomas and 10 non-neoplastic mucosae. In addition, we examined the correlation of the levels of TSP1 mRNA expression levels with promoter methylation status of TSP1 monitored by methylation-specific PCR as well as P53 mutation status detected by PCR-single-strand conformation polymorphism. Promoter hypermethylation of the TSP1 gene was found in 10 (33%) of 30 gastric carcinomas, and TSP1 mRNA expression levels were associated with promoter hypermethylation of TSP1 (p = 0.017; Mann-Whitney U test). P53 mutation was found in 5 (17%) of 30 gastric carcinomas, however, TSP1 mRNA expression was not associated with P53 mutation status (p = 0.858; Mann-Whitney U test). There was no correlation between TSP1 mRNA expression levels and T grade, N grade, tumor stage, or histological type. Our results suggest that transcriptional inactivation of TSP1 by aberrant DNA methylation of the promoter region may participate partly in stomach carcinogenesis through TSP1 down-regulation.

DNA Methylation↗
PubMed2003

Helicobactor pylori infection is closely associated with telomere reduction in gastric mucosa.

OBJECTIVE: To investigate differential reduction in telomere DNA in tissue components of gastric mucosa with respect to Helicobactor pylori infection. MATERIALS AND METHODS: The telomere content was examined by fluorescent in situ hybridization with the (TTAGGG)(4) probe. To compare the signal intensities from the probe (telomere volume) with telomere length, five gastric carcinoma cell lines were used. Telomere volumes were examined in 9 healthy persons, 124 non-cancer patients, and 86 gastric cancer patients. RESULTS: Telomere volume showed a linear correlation with telomere length measured by Southern blotting in gastric carcinoma cells. In healthy persons without H. pylori infection, the telomere volumes of gastric epithelial tissues were 70-79% that of intramucosal lymphocytes (internal control). In 124 patients without gastric cancer, telomere volume of H.-PYLORI-infected mucosa was significantly less than that of H.-pylori-negative mucosa in both metaplastic and non- metaplastic tissues (p < 0.0001). In 86 gastric cancer patients, telomere volumes in intestinal metaplasia adjacent to cancer were 75% that of intestinal metaplasia of non-cancer patients (p = 0.0001). hTERT expression was detected in 6 cancer-associated and 2 cancer-negative intestinal metaplasia specimens, in which telomere volume was markedly reduced. CONCLUSION: H. pylori infection is closely associated with telomere reduction in gastric epithelium.

Blotting, Southern↗
PubMed2003

Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human gastric carcinomas.

The purpose of this study was to investigate the role of interactions between tumor cells and macrophages during angiogenesis in human gastric carcinomas. Macrophage infiltration into tumors and monocyte chemoattractant protein-1 (MCP-1) expression was assessed in 72 archival specimens of gastric carcinoma for comparison with tumor vascularity. The mRNA expression of MCP-1 was examined by RT-PCR in 6 gastric carcinoma cell lines and in fresh biopsy specimens from 18 patients. Immunolocalization of representative angiogenic factors, vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) was also done. MCP-1 expression in tumor cells increased with the depth of tumor invasion (Tis 9.5%, T1 19.4%, T2-4 60.0%), as did microvessel density and macrophage infiltration. Macrophage counts correlated with vessel counts, and both were significantly higher in MCP-1-positive than in negative tumors. Of the 6 gastric carcinoma cell lines, 2 constitutively expressed MCP-1 mRNA. In 6 (33.3%) of 18 biopsy samples, MCP-1 mRNA was expressed at higher levels in tumor tissues than in normal mucosa. VEGF protein was expressed by gastric carcinoma cells, whereas PD-ECGF protein was expressed mainly by stromal mononuclear cells. MCP-1 expression correlated significantly with VEGF but not PD-ECGF expression in gastric carcinomas. These results suggest that MCP-1 produced by human gastric carcinoma cells plays a role in angiogenesis via macrophage recruitment and activation.

Carcinoma↗
PubMed2003

Correlation of a single nucleotide polymorphism in the E-cadherin gene promoter with tumorigenesis and progression of gastric carcinoma in Japan.

A C/A single nucleotide polymorphism (SNP) in the E-cadherin gene promoter has been shown to affect transcriptional efficiency in vitro. In this study, we analyzed the C/A SNP in 106 gastric carcinoma cases and 90 cancer-free controls compared with clinicopathological parameters. The genotype of C/C, C/A, and A/A was found in 61 (58%), 34 (32%) and 11 (10%) of 106 gastric carcinoma cases and in 32 (36%), 52 (58%) and 6 (6%) of 90 cancer-free controls, respectively. The genotype of C/C was significantly more frequent in gastric carcinoma cases than in cancer-free controls (p<0.05). The E-cadherin protein expression level in non-neoplastic gastric mucosa was higher in the C/C genotype than in the C/A. In gastric carcinoma cases, the genotype of C/C was significantly more frequent in the cases of poorly differentiated adenocarcinoma (31/44; 70%) than in well differentiated type (30/62; 48%). The C/C genotype was also significantly more frequent in the cases with deep invasion (51/74; 69%) and with lymph node metastasis (38/54; 70%) than in those confined superficially (10/32; 31%) and without lymph node metastasis (23/52; 44%), respectively (p<0.05). These results suggest that the C/A SNP in the E-cadherin promoter may be a good marker for malignancy of gastric carcinomas.

Aged↗
PubMed2003

Promoter methylation of cyclin D2 gene in gastric carcinoma.

Methylation of CpG island in the promoter has been recognized as an important mechanism for regulation of gene expression. Although considerable work has been done on the epigenetic control of tumor suppressor genes, little is known about the potential role of promoter CpG demethylation in the activation of oncogenes. The cyclin D2 gene is overexpressed in a subset of gastric carcinoma. To determine whether hypomethylation of cyclin D2 is involved in stomach carcinogenesis, we studied methylation of CpG islands in the cyclin D2 gene by methylation-specific PCR in 34 gastric carcinoma specimens, 21 corresponding non-neoplastic mucosae, and 8 gastric carcinoma cell lines. We also measured levels of cyclin D2 mRNA in 23 of the gastric carcinoma cases and in the gastric carcinoma cell lines. Hypomethylation of the cyclin D2 promoter was found in 24 (71%) of the 34 tumor tissues and in 6 (29%) of the 21 corresponding non-neoplastic mucosa, the incidence being significantly different (p=0.002; Fisher's exact test). Moreover, hypomethylation of cyclin D2 was more common in stage III and IV tumors than in stage I and II tumors (p=00.014; Fisher's exact test). All of three cell lines with promoter hypomethylation expressed detectable levels of cyclin D2 mRNA. Treatment of cyclin D2-negative cells lines harboring promoter hypermethylation with demethylating agent, 5-Aza-2'-deoxycytidine, led to a reactivation of cyclin D2 expression. These results suggest that DNA hypomethylation is a mechanism underlying the increased expression of cyclin D2 in cancer cells and that demethylation of cyclin D2 may be involved in development and progression of gastric carcinoma.

Adult↗
PubMed2002

Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma.

Integrin-linked kinase (ILK), a serine/threonine protein kinase, implicates in cellular control of cell-matrix interactions and cell proliferation that is associated with a highly invasive phenotype of certain tumors. To study whether ILK is involved in the development and progression of gastric carcinoma, we examined the expression of ILK in gastric carcinoma cell lines, primary gastric carcinomas and corresponding non-neoplastic mucosa using reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry and analyzed the relationship with clinicopathological parameters. The expression of ILK mRNA was detected in 4 of 5 gastric carcinoma cell lines and 22 of 35 (63%) microdissected tumor samples of primary gastric carcinoma using RT-PCR. The incidence of cases with ILK mRNA expression was significantly higher in scirrhous and intermediate type (82%) than in medullary type (44%) (P=0.0204). Significant association was detected between ILK mRNA expression and presence of nodal metastasis (P=0.0388). Immunohistochemically, strong expression of ILK protein (over 50% of tumor cells were positive) was detected in 69% (84/122) of primary gastric carcinomas, whereas no ILK expression was found in non-neoplastic gastric epithelia. Strong expression of ILK protein was significantly associated with scirrhous and intermediate type (P=0.0217), deep invasion of tumor cells in gastric wall (P=0.0006), and presence of nodal metastasis (P=0.0176). These results strongly suggest that ILK may participate not only in stomach carcinogenesis especially of scirrhous and intermediate types but also in invasion and metastasis of gastric carcinoma. ILK might be a novel molecular marker for aggressive gastric cancer.

Adenocarcinoma↗
PubMed2002

Monocyte chemoattractant protein-1 expression correlates with macrophage infiltration and tumor vascularity in human esophageal squamous cell carcinomas.

Tumor angiogenesis requires the production of angiogenic factors by tumor and stromal cells. Macrophages are key effectors of angiogenesis and reported to contribute to tumor angiogenesis in several carcinomas. To investigate interactions between tumor cells and macrophages in angiogenesis, we examined macrophage infiltration, tumor vascularity and expression of monocyte chemoattractant protein (MCP)-1, CC chemokine receptor 2 (CCR2) and vascular endothelial growth factor (VEGF) in 57 archival specimens from patients with esophageal dysplasia (n = 9) and squamous cell carcinomas (n = 48). Expression of MCP-1 mRNA was also examined by reverse transcriptase-polymerase chain reaction (RT-PCR) in 7 esophageal carcinoma cell lines and fresh biopsy specimens from 14 patients. The number of infiltrating macrophages correlated closely with expression of VEGF by tumor cells and with neovascularization. Of the 7 cell lines, 4 (TE-1, 3, 5 and 13) constitutively expressed MCP-1 mRNA. In 9 (64.3%) of the 14 patients, MCP-1 mRNA was expressed at high levels in tumor tissues as compared to normal mucosa. MCP-1 immunoreactivity increased with the depth of tumor invasion (Tis 0%, T1 26.3%, T2, T3 42.1%). Moreover, macrophage and vessel counts were significantly higher in MCP-1-positive tumors than in MCP-1-negative tumors. Normal and dysplastic esophageal squamous epithelium showed no staining or faint cytoplasmic staining of MCP-1. Expression of CCR2 immunoreactivity was detected in the cytoplasm of mononuclear cells but not of vascular endothelial cells. These results suggest that interactions between cancer cells and macrophages are important for tumor angiogenesis. MCP-1 may play a role in progression of human esophageal carcinoma through its role in angiogenesis.

Carcinoma, Squamous Cell↗