Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of high-metastatic Lewis lung carcinoma A11 cells with sodium orthovanadate, a phosphotyrosine phosphatase inhibitor, resulted in a dose- and time-dependent suppression of cell spreading on various extracellular matrix components such as Matrigel, fibronectin, laminin and type IV collagen, while the treatment did not significantly inhibit attachment of the cells to these substrates. Orthovanadate slightly and reversibly inhibited the in vitro cell growth of A11 cells, but the suppression of cell spreading was not directly due to the inhibition of cell growth. Orthovanadate-treated A11 cells showed reduced invasive ability in a reconstituted basement membrane invasion assay and experimental metastatic ability. Protein tyrosine phosphorylation level in A11 cells was elevated after treatment with orthovanadate. The increase in tyrosine phosphorylation level was partially diminished by the tyrosine kinase inhibitor ST638, concomitantly with restoration of the suppressed cell spreading as well as invasive and metastatic abilities. These results suggest that protein tyrosine phosphorylation influences invasive and metastatic potential of tumor cells possibly through regulating cell-substrate adhesion.
 ...
PMID:Suppression of metastatic potential of high-metastatic Lewis lung carcinoma cells by vanadate, an inhibitor of tyrosine phosphatase, through inhibiting cell-substrate adhesion. 903 Feb 44

Cryosections of normal adult lung (n = 7) and pulmonary epithelial tumors, including squamous (n = 8), adeno (n = 8), bronchioloalveolar (n = 5), and large cell (n = 4) carcinomas (SCC, ACC, BAC, LCC), carcinoids (Cd, n = 7), and neuroendocrine carcinomas (NEC) of variable grades (n = 14) were immunostained by the avidin-biotin peroxidase (ABC) method with monoclonal antibodies to the alpha1-6 and alpha(v) and the beta1-4 integrin subunits. Normal adult alveolar septae showed variably intense immunoreactivity for alpha1,3,6 and beta1, whereas reactions for alpha5 and alpha(v) were weaker and uneven; the remaining integrin subunits were not detected. Bronchial and bronchiolar epithelium showed variably intense staining for alpha2.3,6,v and beta1,4. Reactions were often, though not invariably, basally polarized. SCC, ADC, and LCC showed variably intense reactions for alpha2.3,6,v and beta1,4. BAC were strongly and uniformly stained for alpha1.3 and beta1. In Cd, alpha1,2,3,v and beta1 reactions were noted, whereas in NEC, weak alpha1,3 and beta1 staining was detected with only traces of alpha6 and alpha(v). We conclude that alveolar epithelial cells do not express the hemidesmosome-associated, laminin-binding integrin alpha6beta4 of the bronchial epithelium but rather the alpha1beta1 and alpha3beta1, collagen IV, and laminin receptors, respectively. SCC, ADC, and sampled LCC express an integrin repertory qualitatively similar to that of the bronchial epithelium. Distinct from the latter, the integrin repertory of BAC parallels that of the alveolar epithelium by its strong expression of the multipotential alpha1beta1 and alpha3beta1 integrins. NEC tumors do not display the laminin receptors alpha6beta4 and alpha6beta1 shown by SCC and ADC but express instead alpha1beta1, a collagen IV-laminin receptor rarely found in epithelial neoplasms except for BAC. In NEC tumors, integrins, especially alpha2, decrease with dedifferentiation. Notably distinct from epithelial mesotheliomas, the major fibronectin-binding integrin alpha5beta1 was not found in any type of lung carcinoma.
 ...
PMID:Immunolocalization of integrins in the normal lung and in pulmonary carcinomas. 930 25

Fibronectin concentrations both in plasma and pleural effusion were prospectively determined in 60 patients with exudative pleural effusions. Fibronectin concentrations in plasma and pleural fluid in 12 patients with infectious and exudative pleural effusions (mean +/- SD) were 240 +/- 103 and 212 +/- 115 micrograms.mL-1, in 17 patients with primary or metastatic lung carcinoma 242 +/- 104 and 210 +/- 82 micrograms.mL-1, in 13 patients with pleural tuberculosis 246 +/- 77 and 231 +/- 133 micrograms.mL-1, and in 18 patients with confirmed malignant pleural mesothelioma 261 +/- 119 and 276 +/- 188 micrograms.mL-1. There were no significant differences either in the plasma or serum concentrations of fibronectin between groups (p > 0.05). Although pleural fluid fibronectin content appeared to have high specificity (85%), it was found to be an inefficient biological marker for differentiating nonmalignant from malignant pleural effusions due to its low sensitivity (6%).
 ...
PMID:Assessment of the value of fibronectin as a tumour marker in malignant pleural mesothelioma. 940 61

We have previously reported that (-)-epigallocatechin gallate (EGCg) inhibited lung carcinoma cell adhesion to fibronectin (FN) and demonstrated its interaction with FN. In the present work, we studied the interaction between thermolysin fragments of FN and EGCg. An amino acid sequence analysis of the fragment bound by EGCg-agarose provided its identification as a carboxyl-terminal heparin-binding domain. Thus, the inhibition of cancer cell adhesion to FN by EGCg is not caused by its direct binding to the cell-binding domain containing an Arg-Gly-Asp-sequence.
 ...
PMID:Interaction between the carboxyl-terminal heparin-binding domain of fibronectin and (-)-epigallocatechin gallate. 964 40

A factor that stimulates migration of lung carcinoma cells on biological substrata was purified from the human lung adenocarcinoma cell line WART. A partially purified autocrine motility factor-like substance, termed haptotaxin, was added to the lower compartment of Boyden chambers and the filters were coated on the upper, lower or both sides with different concentrations of the extracellular matrix (ECM) components fibronectin, laminin or collagen type IV. These adhesive proteins coated on the lower surface of the filter promoted the migration (haptotaxis) of lung carcinoma cells. This effect was greatly enhanced by the addition of haptotaxin. In contrast, ECM components (including gelatin) coated on the upper surface or on both filter surfaces did not stimulate tumor cell migration. However, the addition of haptotaxin also timulated cell migration under these conditions. Haptotaxin did not stimulate migration on filters coated with bovine serum albumin or on uncoated filters. Haptotaxin could not be absorbed by fibronectin, laminin, collagen type IV or gelatin, and soluble ECM components did not affect the locomotor effect of haptotaxin. Substrata coated with fibronectin, laminin and collagen type IV induced adhesion and spreading of lung carcinoma cells in a dose dependent fashion. Haptotaxin potentiated adhesion and spreading of tumor cells on these substrata but did not in itself mediate adhesion and spreading of the cells. Anti-VLA 2 antibodies inhibited migration to haptotaxin on gelatin and laminin coated filters but did not affect haptotaxin-induced migration on fibronectin or collagen type IV substrata. Anti-VLA-5 monoclonal antibodies inhibited haptotaxin-induced migration on fibronectin coated filters but not such migration on filters coated with other ECM molecules showing that tumor cells must interact specifically with ECM components in order to migrate to haptotaxin.
 ...
PMID:A tumor derived motility factor that stimulates cell migration on extracellular matrix. 967 77

We previously showed that thyroid carcinoma distinctively expresses intracellular fibronectin (FN) compared to other carcinomas. To determine the persistency of such FN accumulation in metastasis, we immunohistochemically examined the accumulation of intracellular FN in 92 cases of different carcinomas originating from the thyroid gland, lung and kidney, 44 of which showed metastasis to other organs. In all of the cases, normal epithelial cells adjacent to carcinomas did not show intracellular FN. Almost all of the cases (31/32) of thyroid carcinoma with/without metastasis to the lung and/or kidney showed intracellular FN in both the primary and metastatic lesions. Few cases (2/38) of lung carcinoma and none of the 22 cases of kidney carcinoma showed intracellular FN in the primary and metastatic lesions. In conclusion, the intracellular accumulation of FN acquired after carcinogenic transformation is not a common phenomenon in carcinomas, but rather is distinctive for thyroid carcinoma, even when it metastasizes to other organs. The immunohistochemical detection of intracellular FN may be useful for diagnosing thyroid carcinoma, even in metastatic lesions.
 ...
PMID:Retention of intracellular fibronectin expression in primary and metastatic thyroid carcinoma: an immunohistochemical study. 1007 72

Tumor cell attachment to endothelial cells (ECs) is an important step in the metastasis of small cell lung carcinoma (SCLC). Tumor necrosis factor-alpha (TNF-alpha) stimulation of ECs increases the attachment of some malignant cell types to ECs by affecting the expression of cell adhesion molecules (CAMs). Similarly, the inhibition of EC protein kinase C (PKC) and tyrosine kinase (TK) pathways modulates TNF-alpha-mediated effects on CAM expression. We hypothesized that TNF-alpha would increase SCLC attachment to ECs by affecting CAM expression through activation of PKC and TK pathways. To test this hypothesis, human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-alpha (0 to 500 U/mL) for variable time periods (1 to 24 hours), and the attachment of H82 cells (an SCLC cell line) to the HUVECs was quantified. TNF-alpha stimulation of the HUVECs increased H82 attachment from 28.1% +/- 1.6% to 48.8% +/- 1.7% (P < .05). Preincubation of HUVECs with the PKC inhibitors bis-indolylmaleimide (BIN) or calphostin C or the TK inhibitors genistein or herbimycin A (HMA) blocked the TNF-alpha-induced increase in H82 cell attachment. The addition of antibodies to vitronectin (Vn) or beta1-integrin to TNF-alpha-activated HUVECs before the addition of the H82 cells also significantly decreased H82 attachment, whereas the addition of antibodies to E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), neural cell adhesion molecule (NCAM), sialyl-Lewis(x), fibronectin (Fn), alpha(v)-integrin, alpha3-integrin, alpha4-integrin, or alpha5-integrin had no effect on SCLC attachment. In summary, the TNF-alpha-mediated increase in SCLC attachment to ECs appears to be mediated by the activation of EC PKC and TK pathways as well as through effects on the function or expression of EC Vn and beta1 integrin.
 ...
PMID:Tumor necrosis factor-alpha stimulates attachment of small cell lung carcinoma to endothelial cells. 1007 59

Angiogenesis is a characteristic feature of many aggressive tumors and of other relevant disorders. Molecules capable of specifically binding to new-forming blood vessels, but not to mature vessels, could be used as selective vehicles and would, therefore, open diagnostic and therapeutic opportunities. We have studied the distribution of the ED-B oncofetal domain of fibronectin, a marker of angiogenesis, in four different tumor animal models: the F9 murine teratocarcinoma, SKMEL-28 human melanoma, N592 human small cell lung carcinoma, and C51 human colon carcinoma. In all of these experimental models we observed accumulation of the fibronectin isoform containing the ED-B domain around neovascular structures when the tumors were in the exponentially growing phase, but not in the slow-growing phase. Then we performed biodistribution studies in mice bearing a subcutaneously implanted F9 murine teratocarcinoma, using a high-affinity human antibody fragment (L19) directed against the ED-B domain of fibronectin. Radiolabeled L19, but not an irrelevant anti-lysozyme antibody fragment (D1.3), efficiently localizes in the tumoral vessels. The maximal dose of L19 accumulated in the tumor was observed 3 hours after injection (8.2% injected dose per gram). By virtue of the rapid clearance of the antibody fragment from the circulation, tumor-to-blood ratios of 1.9, 3.7, and 11.8 were obtained at 3, 5, and 24 hours, respectively. The tumor-targeting performance of L19 was not dose-dependent in the 0.7 to 10 microg range of injected antibody. The integral of the radioactivity localized in tumoral vessels over 24 hours was greater than 70-fold higher than the integral of the radioactivity in blood over the same time period, normalized per gram of tissue or fluid. These findings quantitatively show that new-forming blood vessels can selectively be targeted in vivo using specific antibodies, and suggest that L19 may be of clinical utility for the immunoscintigraphic detection of angiogenesis in patients.
 ...
PMID:A high-affinity human antibody that targets tumoral blood vessels. 1038 13

The present study provides direct evidence that syndecan 2 participates selectively in the induction of stress fiber formation in cooperation with integrin alpha5beta1 through specific binding of its heparan sulfate side chains to the fibronectin substrate. Our previous study with Lewis lung carcinoma-derived P29 cells demonstrated that the cell surface heparan sulfate proteoglycan, which binds to fibronectin, is syndecan 2 (N. Itano et al., 1996, Biochem. J. 315, 925-930). We here report that in vitro treatment of the cells by antisense oligonucleotide for syndecan 2 resulted in a failure to form stress fibers on fibronectin substrate in association with specific suppression of its cell surface expression. Instead, localization of actin filaments in the cytoplasmic cortex occurred. A similar response of the cells was observed when the cells were treated to eliminate functions of cell surface heparan sulfates, including exogenous addition of heparin and pretreatment with anti-heparan sulfate antibody, F58-10E4, and with proteinase-free heparitinase I. Size- and structure-defined oligosaccharides prepared from heparin and chemically modified heparins were utilized as competitive inhibitors to examine the structural characteristics of the cell surface heparan sulfates involved in organization of the actin cytoskeleton. Their affinity chromatography on a column linked with a recombinant H-271 peptide containing a C-terminal heparin-binding domain of fibronectin demonstrated that 2-O-sulfated iduronates were essential for the binding. Inhibition studies revealed that a heparin-derived dodecasaccharide sample enriched with an IdoA(2OS)-GlcNS(6OS) disaccharide completely blocked binding of the syndecan 2 ectodomain to immobilized H-271 peptide. Finally, the dodecasaccharide sample was shown to inhibit stress fiber formation, triggered by adhesion of P29 cells to a CH-271 polypeptide consisting of both the RGD cell-binding and the C-terminal heparin-binding domains of fibronectin in a fused form. All these results consistently suggest that syndecan 2 proteoglycan interacts with the C-terminal heparin-binding domain of fibronectin at the highly sulfated cluster(s), such as [IdoA(2OS)-GlcNS(6OS)](6) present in its heparan sulfate chains, to result in the induction of stress fiber formation in cooperation with integrin alpha5beta1.
 ...
PMID:Participation of syndecan 2 in the induction of stress fiber formation in cooperation with integrin alpha5beta1: structural characteristics of heparan sulfate chains with avidity to COOH-terminal heparin-binding domain of fibronectin. 1077 16

To investigate the cellular functions of sulfated glycosphingolipids, we introduced the cerebroside sulfotransferase (CST) gene into J5 cells, a subclone of 3LL Lewis lung carcinoma cells. The J5 cells lack acidic glycosphingolipids but accumulate their common biosynthetic precursor, lactosylceramide. We established the stable CST transfectants, J5/CST-1 and J5/CST-2 clones, highly expressing sulfated lactosylceramide (SM3). Both clones exhibited more spherical morphology in comparison to mock transfectant, and their adhesiveness to fibronectin and laminin was significantly lower. The loss of cell-substratum interactions in these SM3-expressing cells could be attributed to decreased expression of integrins (alpha(5), alpha(6), and beta(1)) on the cell surface and their whole cellular levels. However, the levels of H-2K(b) and H-2D(b) antigens remained unchanged. Reverse transcriptase-polymerase chain reaction and Northern blot analyses for these integrins exhibited significant decrease of beta(1) gene expression in J5/CST-1 and 2, but there was no change in the levels of alpha(5) and alpha(6) transcripts. Deglycosylation by endoglycosidase H treatment clearly demonstrated that the precursor form of beta(1) integrin, possessing high mannose oligosaccharide chains, was preferentially decreased in the CST transfectants. These results demonstrate that endogenous SM3 negatively regulates beta(1) integrin expression at the transcriptional level, and the decrease of alpha integrin proteins in the CST transfectants was due to the post-transcriptional modification. We suggest the putative importance of the intracellular pre-beta(1) integrin pool for normal integrin maturation and subsequent function. Although the rates of cell proliferation in vitro for mock and CST transfectants were similar, tumorigenicity of J5/CST-1 and -2 cells inoculated into syngeneic C57/BL6 mice was greatly decreased or even absent. This was probably due to global loss of the efficient cell-matrix interactions, which are essential for the development of malignant tumors in vivo. Thus, we showed the evidence that cellular SM3 negatively regulates the cell-substratum interaction, resulting in the loss of tumorigenicity.
 ...
PMID:Suppression of integrin expression and tumorigenicity by sulfation of lactosylceramide in 3LL Lewis lung carcinoma cells. 1135 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>