Abstract：
:Angiostatin4.5 (AS4.5) is a naturally occurring human angiostatin isoform, consisting of plasminogen kringles 1-4 plus 85% of kringle 5 (amino acids Lys78 to Arg529). Prior studies indicate that plasminogen is converted to AS4.5 in a two-step reaction. First, plasminogen is activated to plasmin. Then plasmin undergoes autoproteolysis within the inner loop of kringle 5, which can be induced by a free sulfhydryl donor or an alkaline pH. We now demonstrate that plasminogen can be converted to AS4.5 in a cell membrane-dependent reaction. Actin was shown previously to be a surface receptor for plasmin(ogen). We now show that beta-actin is present on the extracellular membranes of cancer cells (PC-3, HT1080, and MDA-MB231), and beta-actin can mediate plasmin binding to the cell surface and autoproteolysis to AS4.5. In the presence of beta-actin, no small molecule-free sulfhydryl donor is needed for generation of AS4.5. Antibodies to actin reduced membrane-dependent generation of AS4.5 by 70%. In a cell-free system, addition of actin to in vitro-generated plasmin resulted in stoichiometric conversion to AS4.5. Annexin II and alpha-enolase have been reported to be plasminogen receptors, but we did not demonstrate a role for these proteins in conversion of plasminogen to AS4.5. Our data indicate that membrane-associated beta-actin, documented previously as a plasminogen receptor, is a key cell membrane receptor capable of mediating conversion of plasmin to AS4.5. This conversion may serve an important role in regulating tumor angiogenesis, invasion, and metastasis, and surface beta-actin may also serve as a prognostic marker to predict tumor behavior.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Wang H,Schultz R,Hong J,Cundiff DL,Jiang K,Soff GAdoi
10.1158/0008-5472.can-03-1862subject
Has Abstractpub_date
2004-01-01 00:00:00pages
162-8issue
1eissn
0008-5472issn
1538-7445journal_volume
64pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-06-15 00:00:00
abstract：:The regulation of urokinase secretion and receptor display in a well-differentiated colon carcinoma cell line, GEO, adapted to serum-free conditions was examined. In protein-free medium, the cell line secreted 0.8 +/- 0.1 ng/ml/10(6) cells of urokinase in a 3-day period as determined by an enzyme-linked immunosorbent ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-04-15 00:00:00
abstract：:Prostate cancer is the most common cancer in men in America. Currently, steroid receptor coactivators have been proposed to mediate the development and progression of prostate cancer, at times in a steroid-independent manner. Steroid receptor coactivator-3 (SRC-3, p/CIP, AIB1, ACTR, RAC3, and TRAM-1) is a member of th...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-4076
更新日期：2005-09-01 00:00:00
abstract：:The pharmacokinetics of UCN-01 after administration as a 72- or 3-h infusion to cancer patients in initial Phase I trials displayed distinctive features that could not have been predicted from preclinical data. The distribution volumes (0.0796-0.158 liters/kg) and the systemic clearance (0.0407-0.252 ml/h/kg) were ext...
journal_title：Cancer research
pub_type： 临床试验,杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:Gene-encoded host defense peptides are used as part of the innate immunity, and many of them act by directly lysing the cell membrane of the pathogen. A few of these peptides showed anticancer activity in vitro but could not be used in vivo because of their inactivation by serum. We designed a 15-amino acid peptide, c...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-1438
更新日期：2004-08-15 00:00:00
abstract：:Some of the unexplained aspects of HIV/AIDS epidemiology, virology, and pathology (6, 13) may thus be due to a lack of knowledge of the basic virology of the virus complex and its pathological interaction with cells of the host. There may be no need to call upon anomalous immune responses, vicious transactivating acti...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-04-15 00:00:00
abstract：:The expression of cytochrome P450 genes directly within target cells is an important determinant of human susceptibility to cancers, birth defects, and other chemically initiated diseases. One pivotal gene, CYP1A1, codes for an inducible cytochrome P450 isozyme (P450IA1) responsible for the bioactivation of numerous c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-07-15 00:00:00
abstract：:Somatostatin receptors (SSTR) are highly expressed in well-differentiated neuroendocrine tumors (NET). Octreotide, an SSTR agonist, has been used to suppress the production of vasoactive hormones and relieve symptoms of hormone hypersecretion with functional NETs. In a clinical trial, an empiric dose of octreotide tre...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-1199
更新日期：2013-12-01 00:00:00
abstract：:Immunohistochemical localization of CA 125 using murine monoclonal antibody OC 125 was performed on fresh frozen tissue from 44 endometrial adenocarcinomas and 26 benign endometria. Immunohistochemical evaluation incorporated both intensity and distribution of staining (CA 125 HSCORE). Thirty-seven cancers (84%) and 2...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-04-15 00:00:00
abstract：:The development of molecular dosimetry methods will simplify the identification of people at high risk for cancer. A combined monoclonal antibody immunoaffinity chromatography/high performance liquid chromatography method has been devised to isolate and quantify aflatoxin-DNA adducts and other metabolites in rat urine...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-01-15 00:00:00
abstract：:The level of steroid receptors in target cells affects the responsiveness of the cell to the hormone. In mouse AtT-20 cells, it has been shown that chronic glucocorticoid treatment causes a down-regulation of glucocorticoid receptor (GR) levels (F. Svec and M. Rudis, J. Biol. Chem., 256:5984-5987, 1981). The current s...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-04-15 00:00:00
abstract：:In this report, we describe the immunomodulatory characteristics of poly(I,C)-LC, a synthetic, double-stranded nucleic acid polymer, polyinosinic-polycytidylic acid, that is complexed with poly-L-lysine and solubilized by the addition of carboxymethylcellulose. We consistently observed, both in vitro and in vivo, stim...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-03-01 00:00:00
abstract：:Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galect...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-3013
更新日期：2014-07-01 00:00:00
abstract：:The migration of three human prostate tumor epithelial cell lines (TSU-pr1, PC-3, DU-145) in response to secreted protein from a human prostate stromal cell line was investigated by using the modified blind-well Boyden chamber assay. Migrated cells were quantified by spectrophotometrically measuring the concentration ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-03-15 00:00:00
abstract：:We showed that the PEA3 transcriptional factor interacted with LKB1, a serine/threonine kinase, which is somatically mutated in lung cancer. This interaction occurred through the ETS domain of PEA3 and the kinase domain of LKB1. Mutation of LKB1 in lung cancer cells stabilized PEA3. Reintroduction of wild-type (WT) LK...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-2902
更新日期：2006-08-15 00:00:00
abstract：:Fas (CD95/APO-1) is an important mediator of apoptosis. We show that Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 human breast cancer cells become responsive to anti-Fas (CD95) agonistic antibody-triggered apoptosis after pretreatment or cotreatment with vitamin E succinate (VES; RRR-alpha-tocopheryl succinate). In...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-02-15 00:00:00
abstract：:Cancer vaccines may have applications in the therapy and prevention of mammary carcinoma. To investigate such applications, we constructed a recombinant adenoviral vaccine expressing a kinase-inactive mutant form of human HER2 and introduced this into BALB/c wild-type (WT) or HER2 transgenic mice. Here, we report cont...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0493
更新日期：2010-10-01 00:00:00
abstract：:Hypoxia occurs in two forms in tumors. Chronic or diffusion-limited hypoxia is relatively well characterized. In contrast, intermittent or perfusion-limited hypoxia is not well characterized, and it is not known how common it is in tumors. The purpose of this study was to determine whether spontaneous fluctuations in ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Colony-forming capacity of human melanoma cells was investigated in five established cell lines and isolated cells from seven metastatic or recurrent tumors. A single-cell suspension was added to 0.3% agar medium, and colonies were observed over 7 to 21 days. With the five cell lines, colony formation occurred in all ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:Two sublines, SCLC-MOA1 (MOA1) and SCLC-MOA2 (MOA2), were established from the SCLC-MO cell line, which was originally derived from an oat cell type of small cell lung carcinoma (SCLC). SCLC-MO showed typical culture morphology of SCLC, growing as tightly packed floating aggregates, while both MOA1 and MOA2 grew as a ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:A multilaminar alteration of endoplasmic reticulum (ER) has been observed in tumor cells of eight patients with Hodgkin's disease and a patient with histiocytic lymphoma. These multilaminar structures are more numerous in dividing cells and thus appear to arise primarily during mitosis. The stacked membranes in the mu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:Recent technologic advances have permitted higher resolution and more rapid analysis of individual cancer genomes at the single-nucleotide level. Such advances have shown bewildering intertumor heterogeneity with limited somatic alterations shared between tumors of the same histopathologic subtype. Exacerbating such c...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-12-2217
更新日期：2012-10-01 00:00:00
abstract：:Deleted in colorectal cancer (DCC), the receptor for the multifunctional cue netrin-1, acts as a tumor suppressor in intestinal cancer and lung metastasis by triggering cancer cell death when netrin-1 is lowly expressed. Recent genomic data highlighted that DCC is the third most frequently mutated gene in melanoma; we...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-1590
更新日期：2020-02-15 00:00:00
abstract：:Extracellular signal-regulated kinases (ERK) regulate cellular functions in response to a variety of external signals. However, the specific functions of individual ERK isoforms are largely unknown. Hence, we have investigated the specific function of ERK1 in skin homeostasis and tumorigenesis in ERK1 knockout mice. T...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-3129
更新日期：2006-03-01 00:00:00
abstract：:Thyroid-stimulating hormone (TSH) has long been recognized as the major proliferative and functional stimulus for thyroid follicular cells. TSH receptor (TSHR) engagement stimulates the production of cyclic AMP and the subsequent activation of downstream effector molecules, including protein kinase A, S6K1, and Rap1, ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-2471
更新日期：2007-09-01 00:00:00
abstract：:Previous studies have shown that enforced expression of IFN-beta suppressed tumor growth and metastasis. In this report, we determined whether the induction of nitric oxide synthase II (NOS II) gene is required for IFN-beta-mediated antitumor activity using syngeneic mice with intact (NOS II+/+) or genetically disrupt...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses by trimming peptides for presentation by MHC class I (MHC-I) molecules. Herein, we demonstrate that genetic or pharmacological inhibition of ERAP1 on human tumor cell lines perturbs their ability to engage several classes of ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-1643
更新日期：2015-03-01 00:00:00
abstract：:4-Hydroxyandrostenedione (CGP32349; 4-OHA) is a clinically effective treatment for advanced postmenopausal breast cancer by both the parenteral and p.o. routes, as a result of its inhibition of aromatase and consequent suppression of plasma estrogen levels. Thirty patients were randomized to treatment with 250 mg 4-OH...
journal_title：Cancer research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1989-03-01 00:00:00
abstract：:Suppression of synthesis of specific tropomyosin (TM) isoforms occurs commonly in human, murine, and avian fibroblasts transformed by retroviral oncogenes or other modalities. The resulting deficiency or altered distribution of TMs may predispose the cells to microfilament instability and contribute to expression of t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:More than 500 colorectal tumors with clonal chromosomal abnormalities have been reported. Although the pattern of aberrations is nonrandom, no specific primary or secondary karyotypic abnormality has been identified. Also, the chronological order in which the aberrations appear during disease progression is not well k...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-10-15 00:00:00
