Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface adhesion glycoprotein that mediates leukocyte adhesion through interaction with the leukocyte CD11/CD18 adhesion complex. The aim of this study was to determine whether ICAM-1 is expressed by normal or neoplastic colonic epithelial cells. Immunohistochemical studies on human colonic tissue demonstrated focal ICAM-1 expression by colonic carcinomas but not by normal colonic epithelium. ICAM-1 expression by colonic carcinomas showed a positive correlation with the presence of a peritumoral inflammatory infiltrate. Surface expression of ICAM-1 was also observed in HT-29 cultured human colon cancer cells by both immunohistochemistry and enzyme immunoassay. Interferon-gamma and interleukin-1 beta significantly increased ICAM-1 surface expression by HT-29 cells in a dose-dependent manner. Upregulation of ICAM-1 surface expression became evident some hours after cytokine stimulation and was inhibited by both actinomycin D and cycloheximide, indicating a requirement for de novo RNA and protein synthesis. HT-29 monolayers supported adhesion of human lymphocytes as determined by a quantitative 111In-labeled leukocyte adhesion assay. Adhesion was mediated in part via interaction of ICAM-1 on HT-29 cells with lymphocyte function-associated antigen-1 (CD11a/CD18) on lymphocytes, as defined by using blocking monoclonal antibodies. Expression of ICAM-1 and/or other leukocyte adhesion receptors by neoplastic epithelial cells may play a role in directing leukocyte trafficking and leukocyte-epithelial cell interactions in colonic carcinoma.
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PMID:Human colon cancer cells express ICAM-1 in vivo and support LFA-1-dependent lymphocyte adhesion in vitro. 136 41

Clinical and experimental observations suggest that tumor-induced endothelial cell (EC) injury may be one of several initial events in the establishment of tumor metastases. This work investigates tumor-induced EC injury and the interaction between tumor-damaged EC and platelets. We used cultured bovine EC and extracts of four cultured human malignancies. EC injury was assessed by 51Cr and lactic dehydrogenase (LDH) release. Incubation of EC with melanoma, breast carcinoma or lung carcinoma caused significant LDH and 51Cr release, whereas colon cancer seemed ineffective. Increased adhesion of platelets to tumor-injured EC was noted. These observations indicate that certain varieties of tumor cause EC injury. Adhesion of platelets to tumor-injured EC results in the formation of platelet-tumor thrombi at the endothelial surface, an event that may initiate tumor invasion of the vessel wall.
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PMID:Tumor interaction with vascular endothelium. 366 82

Alterations in several classes of adhesion molecules have been implicated in the progression of colorectal cancer. Cell adhesion regulator (CAR) has been identified as a regulator molecule of integrin-dependent cell adhesion. We have explored a possible involvement of the CAR gene in colorectal cancer. Reverse transcription-PCR revealed that CAR expression was detected in normal colonic cells, whereas it was decreased or undetectable in 6 of 13 (46.2%) human colon cancer cell lines. To further study the biological significance of CAR expression in colon cancer cells, a CAR expression vector was introduced into HT-29 cells, in which CAR is not expressed. Adhesion of HT-29 cells to extracellular matrix components was up-regulated by the introduction of CAR. In spite of similar growth properties with the controls, CAR-transfected HT-29 cells showed a significantly reduced spontaneous metastatic potential in nude mice. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated CAR expression in 30 surgical specimen pairs of human colorectal cancer and adjacent noncancerous tissue using semiquantitative reverse transcription-PCR. In 14 of 30 cases (46.7%), CAR expression in cancer was less than one-tenth of that in matched noncancerous tissue. The tumor:normal ratio of CAR expression was significantly lower in patients with lymph node metastasis than in those without it (P < 0.01) and in patients with distant metastasis than in those without it (P < 0.05). CAR expression was significantly lower in more advanced Dukes' stage tumors (P < 0.05). Our results suggest that down-regulation of CAR expression may play an important role in the progression and metastasis of colorectal cancer.
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PMID:Inverse association of cell adhesion regulator messenger RNA expression with metastasis in human colorectal cancer. 875 33

Adhesion receptors on the surface of cancer cells play an important role in tumor cell migration, invasion, and metastasis. A number of specific cell surface-associated molecules that mediate cell-matrix and cell-cell interactions have been characterized, including the family of integrin receptors, the cadherins, the immunoglobulin (IgG) superfamily, a 67-kDa laminin-binding protein, and the CD44 receptor. Changes in the expression and function of these adhesion molecules are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets in diagnosis and therapy. In esophageal cancer a downregulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors. The occurrence of the CD44 standard and the CD44-9v isoform on the surface of gastric cancer cells is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas giving these tumor cells the ability to metastasize in the lymph nodes. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation of the pancreatic tissue while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors and different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas and thus influencing in their metastatic potential. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation could be observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype, and the metastatic abilities of colorectal cancer cells. Analyzing the expression of the E-cadherin receptor in colorectal carcinomas it has been shown that this receptor may serve as an independent prognostic marker in Dukes' stage Colon cancer to identify patients with poor prognosis and designate them for adjuvant therapy after curative surgical treatment.
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PMID:Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. 889 33

Adhesion of metastatic cancer cells at secondary sites is known to be regulated by several families of adhesion proteins, including selectins and integrins. Colon carcinoma cells have been shown to tether to and roll on both stimulated endothelial cells and purified E-selectin. We have demonstrated that HT-29 human colon carcinoma cells adhere specifically to an E-selectin-IgG chimera. Upon adhesion to E-selectin, the amount of tyrosine phosphorylation of several proteins in HT-29 cell lysates increases compared with cells in bovine serum albumin-coated wells on phosphotyrosine Western blots; this increase is statistically significant. This effect is specific for adhesion to E-selectin, since addition of an E-selectin blocking monoclonal antibody (MAb), E3, to the wells causes a statistically significant decrease in tyrosine phosphorylation relative to E-selectin alone on phosphotyrosine Western blots. One protein that is affected this way has been identified as c-src. Kinase assays show a dose-dependent and statistically significant decrease in c-src activity upon adhesion to E-selectin, which correlates with an increase in phosphorylation of Tyr 527, the negative regulatory tyrosine. CnBr digestion of 32P-labeled c-src shows an increase in phosphorylation of tyrosine 527 after adhesion to E-selectin. Our results may identify a signaling pathway involving the E-selectin ligand on HT-29 cells and c-src.
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PMID:Adhesion of HT-29 colon carcinoma cells to E-selectin results in increased tyrosine phosphorylation and decreased activity of c-src. 917 21

Mucin production by human colon cancer cells correlates with liver metastasis in animal models, but it is not known which steps in metastasis depend on specific alterations in mucin synthesis. Clonal variants of cell line LS174T selected for differences in mucin core carbohydrate expression have been further characterized biochemically, and tested for their ability to participate in metastasis-related events. LS-C mucin contains truncated carbohydrates enriched for sialyl Tn and these cells bind to basement membrane matrix to a greater extent than LS-B cells. This binding is partially inhibitable by antibody to sialyl Tn. LS-B produces more fully glycosylated mucin and preferentially binds to hepatic sinusoidal endothelial cells and E-selectin through sialylated peripheral mucin-associated carbohydrate structures. Adhesion of LS-B to endothelial cells is inhibited by neutralizing antibody to E-selectin, and inhibition of glycosylation or desialylation of LS-B mucin abrogates binding to E-selectin in vitro. LS-B cells spontaneously metastasized from cecum to liver and colonized the liver of athymic mice after splenic-portal injection to a significantly greater extent than LS-C, suggesting that expression of peripheral mucin carbohydrate structures is most important for metastasis of human colon cancer cells.
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PMID:Liver metastasis and adhesion to the sinusoidal endothelium by human colon cancer cells is related to mucin carbohydrate chain length. 959 Jan 34

Alterations in several classes of adhesion molecule have been implicated in the progression of colorectal cancer. Cell adhesion regulator (CAR) has been identified as a regulator molecule of integrin-dependent cell adhesion. We have explored the possible involvement of the CAR gene in colorectal cancer. Reverse transcription-PCR revealed that CAR expression was detected in normal colonic cells, whereas it was decreased or undetectable in 6 of 13 (46.2%) human colon cancer cell lines. Adhesion of HT-29 cells to extracellular matrix components was up-regulated by the introduction of CAR. CAR-transfected HT-29 cells showed a significantly reduced spontaneous metastatic potential in nude mice. In 14 of 30 cases (46.7%), CAR expression in cancer was less than one-tenth of that in matched noncancerous tissue. The tumor: normal ratio of CAR expression was significantly lower in patients with lymph node metastases than in those without (p < 0.01) and in patients with distant metastases than in those without (p < 0.05). CAR expression was significantly lower in more advanced Dukes' stage tumors (p < 0.05). Our results suggest that down-regulation of CAR expression may play an important role in the progression and metastasis of colorectal cancer.
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PMID:[Regulation of integrin function in the metastasis of colorectal cancer]. 974 20

We found that phorbol ester-primed THP-1 cells (a human monocyte cell line), which express a scavenger receptor, were stimulated by mucins through the macrophage scavenger receptor, resulting in enhanced secretion of IL-1beta. The activity was abolished by treatment of the mucins with sialidase, indicating that sialic acid is involved in binding. (125)I-Labeled ovine submaxillary mucin could bind to COS 7 cells transfected with cDNA encoding the scavenger receptor. Binding was inhibited by mucins, fucoidan, and polyinosinic acid but not by polycytidylic acid, this being consistent with the characteristics of the scavenger receptor. When phorbol ester-primed THP-1 cells were cocultured with colon cancer cells producing mucins, IL-1beta secreted from the THP-1 cells increased significantly. Adhesion between colon cancer cells and a scavenger receptor transfectant was observed, and binding was inhibited partly by mucins and ligands for the scavenger receptor.
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PMID:Stimulation of macrophages by mucins through a macrophage scavenger receptor. 1052 77

Carcinoembryonic antigen (CEA) has been reported to promote the metastatic potential in some experimental tumors. Adhesion molecules are known to play an important role in the process of metastasis. Cytokines, including interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), which are produced by Kupffer cells, induce endothelial cells to express adhesion molecules. As a result, the present study was designed to investigate whether the interaction between CEA and Kupffer cells accelerated the metastatic potential of tumors in the liver. Kupffer cells isolated from the liver of male BALB/c mice were cultured with CEA, either with or without the addition of a cytokine inhibitor. The levels of IL-1beta and TNF-alpha were examined in a culture medium. An adhesion assay of colon cancer cell lines to human umbilical vein endothelial cells was also performed. When CEA was added to the Kupffer cell culture medium, cytokines were produced. Elevated levels of cytokines appeared to lead to increased rates of adhesion of cancer cells to endothelial cells. However, these phenomena were blocked by the addition of cytokine inhibitors. CEA stimulated Kupffer cells to produce cytokines. An elevated number of cytokines have been proven to promote the expression of adhesion molecules in endothelial cells. These processes are therefore considered to contribute to the metastasis of malignant cells to the liver. These results suggest that cytokine inhibitors may therefore play an important role in the inhibition of hepatic metastasis.
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PMID:Role of carcinoembryonic antigen in the progression of colon cancer cells that express carbohydrate antigen. 1128 55

Physical characteristics of surgical wounds and viable tumor cells shed may differ between open and laparoscopic procedures. Because environmental factors may vary between the laparoscopic milieu and that of open surgical procedures, we sought to characterize the effect of these factors on tumor cell adhesion, an early step in the process of wound implantation. Human SW620 colon cancer cells were placed in matrix-precoated dishes for 30 min at concentrations of 90,000-540,000 cells/well, at 25-37 degrees C, in the native state of the matrix proteins and after drying for 60 min, and in 0-10% serum. As increased pressure has previously been reported to stimulate colon cancer cell adhesion synergistically with serum, we then further partially characterized the serum components responsible for this potentiating effect. The number of adherent cells varied linearly with cells seeded. Adhesion was temperature-dependent, and also was dependent on the matrix conformation. Less adhesion occurred to dry matrix proteins. Serum dose-dependently potentiated SW620 pressure-stimulated adhesion, with a maximal increase in adhesion compared with ambient pressure conditions at 5% serum concentration. Heat inactivating the serum at 60 degrees C for 30 min ablated the effect. Filtration to remove molecules over 10 kDa produced no change in adhesion relative to ambient conditions, but filtration to 100 kDa preserved the serum effect. When the serum was passed over a gelatin-Sepharose column, which binds numerous proteins including fibronectin, the serum effect was lost. Addition of fibronectin to serum-free media did not reconstitute the effect. The environmental factors of warm temperature, moisture, and serum accumulation may contribute to increased colon cancer cell adhesion. However, the most important determinant of malignant adhesion to surgical wounds, laparoscopic or open, is likely to be the size of the tumor cell inoculum. Pressure stimulation of colon cancer cell adhesion is potentiated by heat-labile serum components of molecular weight 10-100 kDa which bind gelatin-Sepharose, and is not fibronectin alone. Irrigating serum from surgical wounds may decrease tumor implantation.
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PMID:Environmental factors of temperature, humidity, serum accumulation, and cell seeding increase colon cancer cell adhesion in vitro, with partial characterization of the serum component responsible for pressure-stimulated adhesion. 1139 24


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