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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This laboratory recently reported that laminin degradation by cultured colon cancer was plasminogen dependent and reflected the presence of urokinase bound to cell surface receptors. (Schlecte, W.; Murano, G.; Boyd D. Cancer Res., 49:6064-6069; 1989). The present study was undertaken to determine the sensitivity of urokinase receptor directed proteolysis to the type I plasminogen activator inhibitor (PAI-1). Colon cancer cell types, that were highly effective in degrading laminin in vitro, elaborated into their conditioned medium an inhibitor which was indistinguishable from PAI-1 on the basis of its performance in reverse zymography, western blotting, and immunoprecipitation assays. A fraction of this PAI-1 was active, as evidenced by complex formation with the active site of radioactive urokinase. Laminin degradation by the colon cancer cells, however, did not appear to be affected by the endogenous inhibitor, since an antibody to the inhibitor, which blocked urokinase-PAI-1 interactions, had little effect on laminin turnover. Further, addition of exogenous PAI-1, activated by guanidine hydrochloride pretreatment, to the colon cancer cells did not perturb laminin degradation. Because laminin degradation by colonic cells was a function of receptor bound urokinase, presumably immobilized plasminogen activator escaped the neutralizing effect of the inhibitor. These data suggest either a shielding effect of the receptor on the plasminogen activator or a physical separation of activator and inhibitor. Either way, for cultured colon cancer at least, laminin degradation directed by urokinase receptor bound plasminogen activator appeared unaffected by the presence of this inhibitor.
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PMID:Insensitivity of laminin degradation directed by receptor bound urokinase to PAI-1 in cultured colon cancer. 239 Apr 19

Serum concentration of laminin was measured radioimmunologically in 96 patients suffering from various malignancies. Laminin levels were significantly elevated in patients with carcinomas and leukemias, but not in patients with sarcomas or lymphomas when compared with healthy controls. A good correlation could be found between serum laminin concentration and response to therapy in patients with carcinoma and leukemia. Elevated laminin levels were associated with a progressive course of the tumor condition. Furthermore, a close correlation has been detected between serum concentrations of laminin and carcinoembryonic antigen (CEA) in patients with carcinoma of the colon. The serum laminin level seems to be a valuable parameter for observation of the course of certain malignancies.
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PMID:Serum concentration of laminin, and course of the disease in patients with various malignancies. 362 57

Laminin has been shown to promote the malignant phenotype and the expression of certain laminin receptors has been correlated with the malignant character of the tumors. Here new cell lines were isolated from a human colon cancer cell line (LCC-C1) based on their adhesiveness to laminin. The laminin-adherent subclone formed large tumors in nude mice, whereas the laminin-nonadherent subclone failed to form sizable tumors. Only the laminin-adherent subclone adhered to laminin and invaded through Matrigel-coated filters. The adhesive and invasive ability of the cells was almost completely blocked by low concentrations (1.0 microgram/ml) of anti-beta 1 integrin antibody. The amounts of total cellular beta 1 integrin protein were similar in the two subclones when compared by Western blot, and the mRNA levels also did not differ. The localization of beta 1 integrin laminin receptor varied in the two subclones; the laminin-adherent subclone showed a linear distribution along the cell-cell junctions, while the laminin-nonadherent subclone did not stain between the cells. Using laminin-Sepharose affinity chromatography, more beta 1 integrin was obtained from the laminin-adherent subclone. These findings suggest that alterations in the affinity of beta 1 integrin for laminin and in its membrane distribution might be involved in the increased tumorigenicity observed in colon cancer cells.
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PMID:Expression of beta 1 integrin in laminin-adhesion-selected human colon cancer cell lines of varying tumorigenicity. 754 73

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

All known laminin isoforms are cross-shaped heterotrimeric molecules, consisting of one heavy alpha chain and two light beta and gamma chains. Recently, a cDNA encoding a new gamma chain from laminin 5 (also known as kalinin) was sequenced. This chain, named gamma 2, showed extended homology to the classical gamma 1 chain but differed from this by lacking the terminal globular domain. Recent data, indicating an important role of the gamma 2 chain gene in establishing adhesion contacts between epithelial cells and basement membranes, prompted us to investigate whether the gamma 2 chain gene is aberrantly expressed in cancer tissue, and if so whether its localization could provide clues to its possible role in cancer dissemination. Routinely processed tissue specimens from 36 cases of human cancer were investigated, including 16 cases of colon adenocarcinoma, 7 ductal mammary carcinomas, 4 squamous cell carcinomas, 3 malignant melanomas and 6 sarcomas. In situ hybridization for the detection of mRNAs for the gamma 2 chain and for the classical laminin chains alpha 1, beta 1, and gamma 1 was performed using S-35 labeled antisense RNA probes. As positive control of the specificity of the gamma 2 chain mRNA detection, two different anti-sense probes derived from two nonoverlapping cDNA clones were used. Malignant cells were found to express the gamma 2 chain in 29 of the 30 carcinomas studied and the expression was particularly high in cancer cells located at the invasion front. In contrast, mesenchymally derived cancer cells in three different types of sarcomas did not express the gamma 2 chain. In colon cancer there was a clear histological correlation between the expression of gamma 2 chain by cancer cells and their engagement in tumor budding processes. Laminin chains alpha 1, beta 1, and gamma 1 were weakly expressed throughout cancerous areas with no apparent correlation to sites of invasion. The aberrant expression of the gamma 2 chain gene seen in invasively growing cancer cells point to a role of this molecule in establishing focal adhesions of cancer cells to the extracellular matrix during their migration through surrounding normal tissue.
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PMID:The gamma 2 chain of kalinin/laminin 5 is preferentially expressed in invading malignant cells in human cancers. 794 70

Transforming growth factor (TGF)-beta 1 modulates the expression of extracellular matrix (ECM) glycoproteins, fibronectin and laminin and the adhesion of Moser colon cancer cells to these glycoproteins. Since adhesion can be altered through expression of cell-surface receptors, binding affinities of adhesion molecules for receptors, or both, we investigated the effect of TGF-beta 1 on the binding properties of fibronectin and laminin to their cell-surface receptors by saturation binding and Scatchard analyses using radiolabeled fibronectin and laminin. Fibronectin bound to its cell-surface receptor with high affinity (Kd = 1.25 x 10(-9) M), Moser cells had approximately 7.1 x 10(4) fibronectin-binding sites per cell. TGF-beta 1 treatment rapidly up-modulated the number of cell-surface fibronectin-binding sites by 1.9-fold. The binding affinity of fibronectin for the receptor, however, was not altered. Laminin was found to bind to a higher-affinity and a lower-affinity receptor. Moser cells expressed approximately 1.1 x 10(3) higher-affinity laminin-binding sites and approximately 3.1 x 10(4) lower-affinity-binding sites per cell. TGF-beta 1 rapidly increased the expression of the higher-affinity sites 3-fold and the lower-affinity sites 5-fold. The binding affinity of both the higher-affinity and lower-affinity laminin receptors increased 3-fold after 2 and 6 hr of TGF-beta 1 treatment respectively. Concurrent with receptor modulation, TGF-beta 1 induced the secretion of fibronectin and laminin from Moser cells. Northern hybridization analyses showed a concurrent stimulation of the expression of the mRNAs for ligands (fibronectin and laminin) and the mRNAs for the integrin species of the fibronectin and laminin receptors (alpha 5 and alpha 6 subunits). Thus the production of fibronectin and laminin and the expression of their receptors were tightly co-regulated by TGF-beta 1.
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PMID:Regulation of fibronectin and laminin receptor expression, fibronectin and laminin secretion in human colon cancer cells by transforming growth factor-beta 1. 819 84

To evaluate the protective effect of different calcium forms against colon carcinogenesis, Wistar rats fed a high-fat diet (24%) were supplemented with different chemical forms of dietary calcium and were intrarectally instilled with N-methyl-N-nitrosourea (NMU). Supplemental calcium was administered at 1.5% mineral (w/w of total diet) complexed with either carbonate, gluconate, or lactate in Groups 2, 3, and 4, respectively. The tumor incidence of colon cancer was compared with a control group (Group 1), fed the same diet without supplemental calcium. Colon carcinoma incidence was 31, 33, 13, and 7% in Groups 1, 2, 3, and 4, respectively. Calcium had a significant protective effect against carcinogenesis, and the maximum protective effect was observed with gluconate and lactate forms. Laminin P1 blood level was measured as a tumor marker. Laminin P1 results were compared with the reference group (Group T), fed a standard diet and not NMU instilled. The serum laminin P1 level was significantly higher (p = 0.0001) in NMU-instilled Groups 1, 2, 3, and 4 (0.24 +/- 0.03, 0.93 +/- 1.43, 0.84 +/- 1.33, and 0.41 +/- 0.34 mU/ml respectively) than in the Reference Group T (0.10 +/- 0.05 mU/ml).
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PMID:Dietary calcium salts as protective agents and laminin P1 as a biochemical marker in chemically induced colon carcinogenesis in rats. 881 89

Laminin promotes the malignant phenotype, and the expression of certain laminin receptors is increased in malignancy. Previously, we demonstrated that a laminin-adhesive subclone of a human colon cancer cell line showed increased tumorigenicity in nude mice and increased affinity of the beta1 integrin for laminin relative to the laminin-non-adhesive subclone. The total amount of either beta1 integrin protein or mRNA did not increase. As levels of the 32/67-kDa laminin receptor (67LR) correlate with malignancy, we examined 67LR expression in the laminin adhesion-selected human colon cancer cells. The laminin-adhesive subclone, which was more tumorigenic in both heterotopic and orthotopic locations than in a laminin-non-adhesive subclone, showed cell-surface membrane staining of 67LR, whereas the laminin-non-adhesive subclone showed cytoplasmic staining of 67LR. No difference in either the amount of 67LR mRNA or the amount of protein was observed in the parental cells than in the laminin-adhesive and non-adhesive subclones. When assayed on a laminin affinity column, more 67LR molecules bound to the column with cell extracts from the laminin-adhesive subclone than was observed with the non-adhesive subclone. These findings suggest that the increased tumorigenicity of laminin adhesion-selected tumour cells might be due to an alteration in the distribution and/or adhesiveness of multiple receptors including 67LR and beta1 integrin.
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PMID:Expression of 32/67-kDa laminin receptor in laminin adhesion-selected human colon cancer cell lines. 945 40

Laminin-5 is an extracellular matrix protein that plays a key role in cell migration and tumor invasion. Cox-2 is an induced isoform of cyclooxygenases that plays an important role in carcinogenesis, suppression of apoptosis, angiogenesis, and metastasis of colon cancer. We report frequent co-expression of cox-2 and laminin-5 at the invasive front of early-stage lung adenocarcinomas. We investigated the expression of cox-2 and laminin-5 immunohistochemically in 102 cases of small-sized lung adenocarcinoma (maximum dimension, 2 cm or less). Cox-2 and laminin-5 were expressed in 97 (95.1%) and 82 (80.4%) cases, respectively. Both were preferentially localized in cancer cells at the cancer-stroma interface, although cox-2 tended to show a diffuse staining pattern in some cases. A comparison of their staining patterns revealed a striking similarity in their distribution in 24 cases, and a partial overlap between their localization in another 20 cases. Moreover, an overall correlation was found between the expression levels of cox-2 and laminin-5 (P = 0.018). To gain insight into the mechanisms that regulate the expression of these proteins, we additionally studied their expression in 58 cases of stage I lung adenocarcinoma, in which p53 status was determined by immunohistochemistry, polymerase chain reaction-single strand conformation polymorphism analysis, and direct sequencing. The results showed that tumors with mutant p53 tended to express more cox-2 than those with wild-type p53 (P = 0.080). Also, tumors that overexpressed p53 had higher levels of cox-2 and laminin-5 than those without p53 overexpression (P = 0.032 and 0.047, respectively). Further immunohistochemical analysis showed that tumors that overexpressed both epidermal growth factor receptor (EGFR) and erbB-2 had higher levels of cox-2 and laminin-5 than those without concomitant overexpression of these proteins (P = 0.014 and P = 0.018, respectively). To see whether EGFR signaling is involved in cox-2 and laminin-5 expression, we further conducted in vitro analyses using six lung adenocarcinoma cell lines (A549, HLC-1, ABC-1, LC-2/ad, VMRC-LCD, and L27). Western blot analyses showed that cox-2 mRNA levels, and to a lesser extent laminin-5 gamma2 mRNA levels, correlated with the expression levels of erbB-2 and the phosphorylated form of MAPK/ERK-1/2 protein. The addition of transforming growth factor-alpha increased both cox-2 and laminin-5 gamma2 mRNA levels in A549, ABC-1, and L27 with different kinetics; the induction of cox-2 occurred earlier than that of laminin-5 gamma2. Finally, the migration of ABC-1 cells was inhibited by MAP kinase kinase inhibitor PD98059 and a selective cox-2 inhibitor NS-398. In contrast, the migration of A549 cells was inhibited by PD98059, but much less effectively by NS-398. These results suggest that co-stimulatory mechanisms may exist that increase the expression of cox-2 and laminin-5 at the invasive front of lung adenocarcinomas and that EGFR signaling could be one of the mechanisms. Further investigations are warranted concerning the role of cox-2 and laminin-5 in cancer cell invasion and the significance of p53 and EGFR signaling in the regulation of cox-2 and laminin-5 expression.
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PMID:Frequent co-localization of Cox-2 and laminin-5 gamma2 chain at the invasive front of early-stage lung adenocarcinomas. 1189 Dec 9

Laminin-332 (Ln-332) is a heterotrimeric glycoprotein (alpha3beta3gamma2) unique to epithelial cells with crucial roles in signaling, adhesion, and migration. Altered localization or expression levels of Ln-332, particularly its gamma2 subunit, are of prognostic value in a variety of cancers. However, the lack of standardized methodology and the limited quantification of previous study results have left unanswered questions, including the role of gamma2 transcript variants and whether differential expression of this chain represents dysregulation of the whole heterotrimer. Herein, we test the hypothesis that mRNA changes in one or more Ln-332 encoding genes can be used to distinguish between early- and advanced-stage cancer specimens and shed light on mechanistic questions raised by previous studies. Statistical analyses of human microarray data from the publicly available expression project in Oncology (expO) dataset, including examination of the distributions of Ln-332 subunit mRNA levels, identified a significant decrease in the Ln-332 beta3:gamma2 mRNA ratio between normal (n = 10) and early-stage colon cancer (n = 29) specimens. The beta3:gamma2 ratio was further decreased in metastatic colon cancer (n = 41) compared with early-stage samples. Our findings raise the possibility that Ln-332 gamma2 may be a therapeutic target against metastatic colon cancer because a lowered beta3:gamma2 ratio would reduce expression of heterotrimeric Ln-332 and increase monomeric gamma2 secretion. Further, standardized, quantitative methods for patient prognosis and therapeutic choice could be developed based upon the Ln-332 mRNA changes we uncovered.
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PMID:A decreased ratio of laminin-332 beta3 to gamma2 subunit mRNA is associated with poor prognosis in colon cancer. 1938 90


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