Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor invasion and metastasis involve the interaction between tumor cells and basement membrane, which is mediated in part by laminin receptors. To search for tumor-associated-genes which can be used as new markers in colon cancers with known poor prognosis, cDNA libraries from a colon cancer cell line and colonic tissues were constructed and screened. We selected a cDNA clone which encodes 32-kD laminin-binding protein (LBP-32), and showed increased mRNA expression of LBP-32 in colon carcinoma. This mRNA expression was also correlated with clinical tumor staging. Furthermore, to investigate the role of LBP-32 in cancer invasion and metastasis, cell adhesion assays and in vitro invasion assays were performed, using anti-sense RNA of LBP-32 to block the synthesis of LBP-32. Results showed that anti-sense RNA of LBP-32 inhibits tumor cell attachment and invasiveness in vitro in transfectants of a colon cancer cell line. These data suggest that LBP-32 may play an important role in colon cancer progression, and that LBP-32 may be used as a marker of biological aggressiveness. These findings also imply that laminin receptors may provide a target for novel therapeutic strategies: modulating LBP-32 expression by anti-sense RNA or monoclonal antibodies may have clinical application in colorectal cancer therapy.
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PMID:[Cellular and molecular biological study of the laminin-binding protein and its clinical application]. 147 Jan 61

Tumor invasion and metastasis involves the interaction between tumor cells and basement membrane, which is mediated in part by laminin receptors/laminin-binding proteins. We have reported that a 32-kDa laminin-binding protein (LBP-32) was overexpressed in colorectal cancer at the messenger RNA (mRNA) level and correlated with clinical staging. However, the function of this protein is not yet defined. In this study, we have analyzed the role of LBP-32 in tumor cell attachment and invasion through various basement membrane components. Blockade of LBP-32 synthesis with an anti-sense RNA was utilized in this study. The partial sequence (237 bp) of LBP-32 was inserted into the EMSV33 vector in the sense or antisense direction. Clone A, a poorly differentiated human colon carcinoma cell line, was transfected with EMSV33 alone (control), or EMSV33 with the insert in sense (LBP-S) or anti-sense (LBP-AS) direction using lipofectin. The cell adhesion assays (at 37 degrees C for 75 min) were performed using parental Clone A cells or the transfectants. Specific attachment to wells coated with laminin, fibronectin, or type IV collagen was evaluated. In vitro cell invasion assays were performed using the parental clone A cells and their transfectants to assess the passage through polycarbonate filters coated with matrigel, a reconstituted basement membrane. The results showed that (a) laminin and collagen IV (but not fibronectin) play a role in colon cancer cell attachment to substrata, and (b) anti-sense RNA of LBP-32 inhibits tumor cell attachment and invasiveness in vitro. These findings suggest a role for LBP-32 in colon cancer progression and metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-sense RNA of 32-kDa laminin-binding protein inhibits attachment and invasion of a human colon carcinoma cell line. 153 86

Cell surface receptors for laminin may play an important role in tumor migration and metastasis. To evaluate laminin receptor/laminin-binding protein expression in human colon carcinoma, surgical specimens of primary colon cancers and liver metastases were examined by blot hybridization of total RNA with a complementary DNA clone which encodes a Mr 32,000 human laminin-binding protein. The mRNA level of the laminin-binding protein was higher in primary colon carcinoma than in adjacent normal colonic epithelium in 20 of 21 cases. In all 6 cases of colon cancer liver metastases, the laminin-binding protein mRNA level was more than 3-fold greater in tumor than in adjacent normal liver tissue. The tumor/normal ratio of this laminin-binding protein mRNA expression in primary colon cancer has significant correlation with Dukes' classification (P less than 0.001). Our results suggest that mRNA expression of the laminin-binding protein may be a marker of human colorectal cancer progression and biological aggressiveness.
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PMID:Expression of a Mr 32,000 laminin-binding protein messenger RNA in human colon carcinoma correlates with disease progression. 214 Dec 94

Laminin, a major basement membrane-specific glycoprotein, promotes the attachment, migration, and invasion of a variety of tumor cells. Since laminin is present in the perisinusoidal matrix of the liver, we studied its effects on liver colonization by human colon cancer cells (HM7, LiM6) previously shown to have liver-metastasizing ability in athymic mice. These malignant cells expressed high levels of a 32-kDa laminin-binding protein on Western blot analysis when compared to the low metastatic parental cell line. Coinjection of laminin alpha chain-derived peptides which contain the amino acid sequence Ile-Lys-Val-Ala-Val (IKVAV) significantly stimulated liver colonization as determined by liver weight (P < 0.005) and number of tumor nodules (P < 0.02) 3 weeks after splenic-portal inoculation into nude mice. No stimulation was seen with a control peptide containing the same amino acids but in a scrambled sequence. In contrast, the Tyr-Ile-Gly-Ser-Arg peptide from the laminin beta 1 chain significantly inhibited HM7 liver colonization. These differences were not due to alterations in the number of cells initially reaching the liver as determined by injection of [125I]iododeoxyuridine-labeled tumor cells, but retention in the liver was stimulated by the IKVAV-containing peptides. Flow analysis indicated that the IKVAV peptide may act, in part, by stimulating homotypic adhesion of tumor cells. These data suggest that interactions of colon cancer cells with the IKVAV site on laminin may play a role in the formation of metastatic foci in the liver through cell-cell or cell-substratum interactions which promote metastasis.
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PMID:The laminin alpha 1 chain Ile-Lys-Val-Ala-Val (IKVAV)-containing peptide promotes liver colonization by human colon cancer cells. 775 2

Colorectal cancer initiation and progression are associated with stepwise genetic alterations. We and others have shown that a gene encoding for a 32-kDa putative laminin-binding protein (LBP-32) is overexpressed during colorectal cancer progression by Northern blots analysis. Northern blots cannot indicate the heterogeneity of expression from cell to cell and the distribution pattern of gene expression within a given tumor. In order to overcome these problems, we examined the LBP-32 mRNA expression in colorectal carcinomas by in situ hybridization. LBP-32 mRNA expression in 30 cases of primary and metastatic colorectal cancers and their respective adjacent normal tissues were detected by in situ hybridization using 35S-UTP radiolabeled antisense riboprobes. The results showed that LBP-32 mRNA was expressed at a low level in the normal colonic mucosa adjacent to the tumor compared with colon cancer tissues. Its expression in poorly differentiated colorectal cancer was much higher than that in well- and moderately differentiated colorectal cancer. More importantly, the LBP-32 mRNA was expressed more highly in the invasive lesions of the cancer and liver metastases compared with the cancer lesions in situ. Our results imply that in situ hybridization is a powerful tool in evaluating the changes in gene expression in the cancer cells and LBP-32 mRNA expression is related to progression, invasion, and metastasis of colorectal cancer.
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PMID:Expression of 32-kDa laminin-binding protein mRNA in colon cancer tissues. 876 53

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