Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The KAI1 gene, located on human chromosome 11p11.2, suppresses tumor metastasis when expressed in certain cancer cells. To evaluate whether dysregulation of KAI1 occurs during the progression of human prostatic cancer, protein expression, mutation, and allelic loss of KAI1 were analyzed using a tissue bank of 98 primary cancers and 32 metastases. By immunohistochemical staining, high levels of KAI1 protein are detected in the epithelial but not stromal compartment of normal prostatic and benign prostatic hyperplasia tissue. In epithelial cells, KAI1 protein is expressed on the plasma membrane. KAI1 protein expression is downregulated in more than 70% of the 49 primary prostatic cancers from untreated patients. In 10 such untreated patients, down-regulation of KAI1 protein occurred in all of the lymph node metastases examined. In 15 patients with metastatic disease who had failed androgen ablation therapy, more than 90% of the primary prostatic cancers had downregulation, with 60% having no KAI1 protein expression. Primers derived from the sequences flanking each exon of KAI1 were used to analyze KAI1 mutation and allelic loss by the method of PLR-single-strand conformational polymorphism. Using this method, no point mutation or allelic loss was detected in metastases from 10 patients. No allelic loss was detected in an additional 34 primary and 12 lymph node metastases via microsatellite analysis using the marker D11S1344, which is located in the region of KAI1. These results demonstrate that KAI1 protein expression is consistently down-regulated during the progression of human prostatic cancer and that this down-regulation does not commonly involve either mutation or allelic loss of the KAI1 gene.
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PMID:Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss. 881 31

KAI1 is a metastasis suppressor gene for prostate cancer that is located on chromosome 11p11.2-13. Using Northern blot analysis and in situ hybridization, we studied expression of KAI1 mRNA in specimens from 14 normal pancreases and 27 primary pancreatic cancers, and then correlated the findings with the clinical and histopathological parameters of the patients. Northern blot analysis showed increased steady-state levels of KAI1 mRNA expression in 24 of 27 (89%) pancreatic cancer samples. In situ hybridization showed enhanced KAI1 mRNA levels in the pancreatic cancer cells in 82% cancer tissues. The stroma surrounding the cancer mass and normal pancreatic tissue adjacent to the cancer cells exhibited very low levels of KAI1 mRNA expression. Correlation of the mRNA levels obtained by Northern blot analysis with clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher (P < 0.01) in earlier tumor stages (I, II), compared with advanced tumor stages (III, IV) in which lymph node or distant metastases were present. Furthermore, poorly differentiated tumors had significantly higher KAI1 mRNA levels than those that were moderately or well differentiated (P < 0.05). No association between KAI1 expression and survival was found. Our results indicate that KAI1 mRNA expression is reduced in patients with advanced tumor stages. This suggests that reduction of KAI1 expression might enable pancreatic cancer cells to spread in lymph nodes and to distant organs.
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PMID:KAI1 expression is up-regulated in early pancreatic cancer and decreased in the presence of metastases. 889 37

Down-regulation of KAI1 mRNA expression has been shown to be associated with the formation of metastases or disease progression in pancreatic cancer. Whether KAI1 possesses similar characteristics in other malignancies of the gastrointestinal tract is not known. Here, we compared the patterns of KAI1 mRNA expression in 41 esophageal cancers and 35 stomach cancers to assess whether KAI1 might also be of biological relevance in the metastatic ability of these tumors. By Northern blot analysis, KAI1 mRNA levels ranged widely in both normal and cancerous esophageal and gastric tissue samples, with no statistical differences. No association between KAI1 mRNA expression and tumor stage or tumor differentiation was seen in these tumors. In addition, KAI1 mRNA expression was similar in primary esophageal and gastric cancer samples with or without metastases. By in situ hybridization, KAI1 mRNA expression was evident in the cytoplasm of most squamous epithelial cells in the normal esophagus and in nonmucosal epithelial cells of the normal stomach. The staining intensity in the esophageal and gastric cancer cells was similar to that in the normal controls. This differential pattern of KAI1 mRNA expression in esophageal and gastric cancers in comparison to pancreatic cancer indicates that KAI1 seems to influence the potential of gastrointestinal cancer cells to metastasize differently. In esophageal and gastric cancers, the formation of metastases is not dependent on the reduction of KAI1 in the cancer cells.
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PMID:KAI1 is unchanged in metastatic and nonmetastatic esophageal and gastric cancers. 948 31

Prostate cancers account for 43% of all cancers diagnosed in American men. It is estimated that in 1996, 317,000 new cases of prostate cancer were diagnosed and 41,000 men died of the disease. The challenge of treating prostate cancer lies in accurately distinguishing those histologically-localized cancers which will complete metastatic progression from those that will remain indolent. At this time, we lack appropriate histological markers to make such distinctions, therefore, it is often difficult to accurately predict the clinical course of an individual patient's disease. There is growing evidence that a critical event in the progression of a tumor cell from a non-metastatic to metastatic phenotype is the loss of function of metastasis-suppressor genes. These genes specifically suppress the ability of a cell to metastasize. Work from several groups has demonstrated that human chromosomes 8, 10, 11 and 17 encode prostate cancer metastasis suppressor activities. As a result of these efforts the first prostate cancer metastasis-suppressor gene, KAI1, was identified and mapped to the p11-2 region of chromosome 11. In subsequent studies, an additional gene encoded by the same region, CD44 was also determined to have metastasis-suppressor activity. Recent studies have shown a correlation between decreased expression of KAI1 and CD44 and an increased malignant potential of prostate cancers. It is anticipated that the identification of other metastasis suppressor genes may allow for the development of diagnostic markers useful in the clinical substaging of individual tumors. This manuscript is intended to present our perspective on the importance of these genes in the understanding of prostate cancer progression. More importantly, we present new findings from our laboratory's effort to identify the metastasis-suppressor genes encoded by human chromosome 17. Specifically we report the strategy currently being used to evaluate a series of candidate genes and the approach being utilized to pinpoint the metastasis-suppressor region on human chromosome 17.
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PMID:Prostate cancer metastasis-suppressor genes: a current perspective. 957 26

Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin-embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by immunohistochemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. In human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin-embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. In some cases, pretreatment with trypsin enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded human tissues were not optimal for determining levels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmic localization of the protein in cells.
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PMID:Expression of KAI1 in paraffin-embedded normal, hyperplastic and neoplastic prostate and prostate carcinoma cell lines. 958 71

KAI1 belongs to a structurally distinct family of membrane glycoproteins, which function via cell-cell and cell-extracellular matrix interactions, thereby potentially influencing the ability of cancer cells to invade tissues and to metastasize into lymph nodes and distant organs. In the present study, we examined KAI1 expression in lymph node and liver metastases in comparison with primary pancreatic cancer to evaluate its influence on metastasis. KAI1 mRNA analysis was performed by Northern blot analysis and in situ hybridization. In addition, the respective protein was studied by immunostaining. Fourteen primary pancreatic cancer samples in which no lymph node metastases were present and 25 primary pancreatic cancer samples in which lymph node metastases were present at the time of tumor resection were included. In 20 of these cases, primary pancreatic cancer tissues and corresponding lymph node metastases from the same patient were studied. Furthermore, 11 liver metastases were available for KAI1 analysis. Increased steady-state levels of KAI1 mRNA were found in 33/39 (85%) primary pancreatic cancers in comparison with normal controls. Statistical analysis of KAI1 mRNA levels and clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher in non-metastasized tumors compared with tumors in which lymph node or distant metastases were present. In lymph node metastases KAI1 mRNA expression was lower than in the corresponding primary tumors: In 14 of 20 lymph node metastases no KAI1 mRNA expression and in 6 of 20 lymph node metastases only weak KAI1 mRNA levels were present in some cancer cells. Cancer cells of distant metastases were devoid of or exhibited low KAI1 mRNA levels compared with those of primary pancreatic cancers. A similar pattern was observed by immunostaining. These data support the hypothesis that KAI1 gene expression might influence the metastatic ability of pancreatic cancer cells in vivo. Reduction of KAI1 appears to promote cancer cell spread in lymph nodes and distant organs.
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PMID:Reduced KAI1 expression in pancreatic cancer is associated with lymph node and distant metastases. 969 25

Down-regulation of KAI1 expression has been shown to be associated with formation of metastases or disease progression in prostate and pancreatic cancer. In the present study we analyzed the expression pattern of KAI1 in metastatic and nonmetastatic hepatocellular carcinomas (HCCs) in comparison with normal livers to evaluate whether alteration of KAI1 also facilitates the metastatic ability in this malignancy. Thirty-nine primary HCCs and 10 normal liver tissue samples were studied for KAI1 messenger RNA (mRNA) expression with use of Northern blot analysis and in situ hybridization. By Northern blot analysis, moderate to strong KAI1 mRNA expression was present in normal liver samples. In contrast, KAI1 mRNA expression in tissue samples of primary HCCs was markedly decreased compared with normal controls. The normal/tumor ratio of KAI1 mRNA expression was 2.6:1 (P <.01). Primary HCCs that gave rise to metastasis showed significantly lower KAI1 mRNA levels than nonmetastasized HCCs (P <. 05). As seen by in situ hybridization, moderate to strong cytoplasmic KAI1 mRNA staining was present in almost all normal hepatocytes. Bile ducts, blood vessels, and connective tissue showed no or only faint KAI1 mRNA expression in the normal liver samples. In nonmetastatic HCCs, the cancer cells exhibited in situ hybridization signals that were similar to the normal controls. In contrast, most of the primary HCC cells in samples with metastases showed only faint or moderate KAI1 mRNA expression predominantly in the perinuclear regions. When KAI1 mRNA expression of primary hepatocellular cancer cells was compared with metastasized cancer cells in lymph nodes, with intrahepatic satellite metastasis, or with peritoneal metastasis in the same patients, significantly lower (P <.01) KAI1 mRNA levels were present in the metastasized HCC cells. Reduced KAI1 mRNA in HCC cells seems to influence their metastatic ability and thereby enhances the malignant potential of HCC.
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PMID:KAI1, a new metastasis suppressor gene, is reduced in metastatic hepatocellular carcinoma. 982 10

KAI1 gene is a novel metastasis suppressor gene. Its transcription level has been reported to be related with metastases in several kinds of tumors. The Authors used RT-PCR method to investigate the expression levels of KAI1 gene in hepatocellular carcinoma (HCC) tissues from 42 patients. The results demonstrated that 57.1% of tumor tissues were positive in KAI1 expression. There was no statistically significant difference on KAI1 gene expression rate between large (>5 cm) and small (<=5 cm) tumors, encapsulated and non-capsulated tumors, as well as alpha-fetoprotein (AFP) positive (>20 ug/ml) and negative (<=20 ug/ml) tumors; however, the expression rate was higher in tumors without intrahepatic metastasis than in those with intrahepatic metastasis (63.9% vs. 16.7%, P<0.05). It is suggested that KAI1 gene expression may be related to the metastases of hepatocellular carcinoma.
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PMID:KAI1 gene expression in hepatocellular carcinoma and its relationship with intrahepatic metastases. 989 67

The metastasis suppressor gene KAI1 was identified by its ability to inhibit the formation of pulmonary metastases in experimental models for prostatic carcinoma. Down-regulation of this gene may be correlated with the invasive phenotype in melanomas and colon and bladder carcinomas and with the metastatic phenotype in carcinomas of the lung, breast, prostate, and pancreas. The goal of our study was to establish an immunohistochemical method to detect KAI1 expression in archival tissues. Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls, we observed strong membrane staining in lymphoid follicular centers and squamous epithelia. We then demonstrated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions. All eight reactive lymph nodes were KAI1 positive. In contrast, three of 13 follicular small cleaved and five of 13 diffuse large cell lymphomas were KAI1 negative. Seventy-nine percent (37 of 47) of invasive squamous cell carcinomas from the lung (n = 15), head and neck (n = 18), and cervix (n = 14) showed extensive KAI1 down-regulation. Loss of KAI1 expression was also found in a subset of 10 high-grade cervical dysplasias. Our data show that (i) immunohistochemistry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and high-grade lymphomas; and (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an important role of the gene in the suppression of invasion in these malignancies.
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PMID:Frequent loss of KAI1 expression in squamous and lymphoid neoplasms. An immunohistochemical study of archival tissues. 1036 91

The KAI1 gene, isolated from human chromosome 11p11.2, has been implicated as a prostate cancer metastasis suppressor gene. Recent studies have demonstrated that the expression of KAI1 protein is reduced in metastases of human prostate cancers and is inversely correlated with tumour grade. The objectives of the present work were to determine whether alterations of KAI1 at a genetic level in localized prostate cancers correlate with degrees of differentiation. This paper reports the application of semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis to two different regions of the KAI1 gene on 35 microdissected primary prostate cancer specimens and demonstrates a biphasic pattern of KAI1 expression according to histological grade. KAI1 mRNA, relative to the housekeeping gene beta -actin, was elevated in low-grade primary prostate cancer (2.7+/-0.4) compared with non-malignant (hyperplastic) prostatic tisues (0.92+/-0.02, p< 0.05), yet reduced in high-grade primary cancers (0.61+/-0.11, p< 0. 05). These data demonstrate, for the first time, that KAI1 is biphasically expressed in primary prostate cancers and suggest that hyperexpression of KAI1 in low-grade prostate cancer may be associated with restraint of tumour progression, whereas a relative decrease in KAI1 gene expression may accompany more aggressive cancers through loss of such restraint. This differential expression of the metastasis suppressor gene KAI1 in primary prostate cancers may have important prognostic implications for the development of subsequent metastases. Should the level of KAI1 in primary prostate cancer be correlated with patient outcome such information may, in the future, enable more intensive adjuvant therapy to be directed to those patients identified to be at greatest risk of metastasis.
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PMID:Expression of the prostate cancer metastasis suppressor gene KAI1 in primary prostate cancers: a biphasic relationship with tumour grade. 1044 Jul 48


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