Abstract:
:Cellular interaction with the extracellular milieu plays a significant role in normal biological and pathologic processes. Excessive degradation of basement membrane matrix by proteolytic enzymes is a hallmark of tumor invasion and metastasis, and aspartyl proteinase cathepsin D is implicated as a major contributor to this process. Maspin, a non-inhibitory serpin, plays an important role in mammary gland development and remodeling. Expression of Maspin is decreased in primary tumors and lost in metastatic lesions. Maspin is mostly cytoplasmic and is partially secreted; however, the fate and function of secreted Maspin has remained mostly unexplored. We hypothesized that secreted Maspin is incorporated into the matrix deposited by normal mammary epithelial cells and thus could play a critical role in cathepsin D-mediated matrix degradation and remodeling of mammary tissue. In the absence of Maspin, as is the case with most cancer cells, matrix degradation proceeds unrestricted, thus facilitating the progression to metastasis. To test this, we employed an in vitro model where gels containing both types I and IV collagen were preconditioned with normal mammary epithelial cells to allow the incorporation of secreted Maspin. This conditioned matrix was used to examine cathepsin D-mediated collagen degradation by human breast cancer cell lines. Our results indicate that secretion of Maspin and its deposition into the extracellular milieu play an important role in matrix degradation. In this capacity, Maspin could potentially regulate mammary tissue remodeling occurring under normal and pathologic conditions. In addition, these findings could have a potential effect on future therapeutic intervention strategies for breast cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Khalkhali-Ellis Z,Hendrix MJdoi
10.1158/0008-5472.CAN-06-4767subject
Has Abstractpub_date
2007-04-15 00:00:00pages
3535-9issue
8eissn
0008-5472issn
1538-7445pii
67/8/3535journal_volume
67pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The purpose of this study was to determine the effect of route of hepatic administration of drug on the regional pharmacokinetics and systemic exposure of 5-fluorouracil (FUra) and 5-bromo-2-deoxyuridine (BrdUrd). A total of 13 mixed-breed male and female dogs were used in these acute studies. Each dog was administere...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-10-15 00:00:00
abstract::Although the concept that cancers originate from stem cells (SC) is becoming scientifically accepted, mechanisms by which SC contribute to tumor initiation and progression are largely unknown. For colorectal cancer (CRC), investigation of this problem has been hindered by a paucity of specific markers for identificati...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4418
更新日期:2009-04-15 00:00:00
abstract::Estrogen receptor (ER)-positive human breast cancer cells are hormonally regulated and are inhibited by retinoids, whereas most ER-negative breast cancer cells are not. Here, we compared retinoid-induced transcriptional activation and growth inhibition in the ER-negative breast cancer cell line MDA-MB-231, stably tran...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-11-15 00:00:00
abstract::Alkaline phosphatase was monitored in 17 mice with s.c.-implanted tumors to relate the total circulating alkaline phosphatase to the total number of tumor cells in each mouse. There was a semilogarithmic relationship between the alkaline phosphatase units and the number of tumor cells. A time-independent standard plot...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-02-01 00:00:00
abstract::The cultivated mushroom of commerce in the Western hemisphere, Agaricus bisporus, was given p.o. to randomly bred Swiss mice for 3 days and was followed by semisynthetic diet for 4 days each week for life. The mice were 6 weeks old at the beginning of the experiment. As a result of treatment, tumors were induced in th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::We used comparative genomic hybridization to study malignant fibrous histiocytomas (MFHs) from 19 patients to detect changes in the copy number of DNA sequences, along entire chromosomes. Together with losses and gains in various chromosomal regions, distinct high-level amplifications were found at six loci (4q12-21, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::DNA polymerase beta (Polbeta) is a DNA repair protein that functions in base excision repair and meiosis. The enzyme has deoxyribose phosphate lyase and polymerase activity, but it is error prone because it bears no proofreading activity. Errors in DNA repair can lead to the accumulation of mutations and consequently ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-0136
更新日期:2004-06-01 00:00:00
abstract::The development of mouse models with the endogenous hypoxanthine-guanine phosphoribosyl transferase (hprt) gene and lacI transgene as mutational targets provides an excellent opportunity to compare the mutant frequency (Mf) and types of mutations induced in vivo in different sequence contexts. To this end, a study was...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-10-15 00:00:00
abstract::Reactive oxygen species play a critical role in the onset of apoptosis induced by various extracellular stimuli, including ionizing radiation. Therefore active regulation of reactive oxygen species-metabolizing enzymes may be one response to an apoptotic stimulus. In this regard, HP100 cells, H(2)O(2)-resistant varian...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00
abstract::Anticancer vaccine strategies can now target intracellular antigens that are involved in the process of malignant transformation, such as oncogene products or mutated tumor suppressor genes. Fragments of these antigens, generally 8-10 amino acids in length and complexed with MHC class I molecules, can be recognized by...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-04-15 00:00:00
abstract::cis-Diammine(1,1-cyclobutanedicarboxylato)platinum (CBDCA) is a nonnephrotoxic but myelosuppressive analogue of cisplatin (DDP) with greatly reduced protein binding and greatly increased renal excretion. Thus, CBDCA might produce undue toxicity in patients with decreased renal function. Twenty-two patients [14 females...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract::Exposure of rats to a standard four-cycle feeding regimen of 0.06% 2-acetylaminofluorene (AAF) results in the formation of putatively premalignant hepatic nodules, but the types and magnitude of DNA adducts formed in these nodules has not been previously examined. By using a sensitive 32P-adduct assay (R. C. Gupta, Ca...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-09-15 00:00:00
abstract::To examine genetic instability during carcinogenesis, we screened 171 carcinomas of the breast, liver, proximal colon, stomach, pancreas, uterine cervix, and ovary for replication error at four microsatellite marker loci on chromosome 2, 3, and 17. A significantly high incidence of genetic instability was observed in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::We have recently demonstrated the consistent detection of transforming growth factor alpha (TGF-alpha) in chemically transformed hamster oral tumors. By Northern blot analysis, no TGF-alpha mRNA can be detected in normal cheek pouch mucosa. The consistent expression of TGF-alpha associated with the malignant transform...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here, we demonstrated that TNFα stimulation induced transcriptional downregulation of MSH2,...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2926
更新日期:2016-08-01 00:00:00
abstract::Several metabolic processes, such as DNA organization and replication, transcription, and RNA processing are closely associated with the nuclear matrix. Nuclear matrix attachment regions are nucleotide sequences holding DNA tightly complexed with the nuclear scaffold and are resistant to extractions with detergents an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::The intracellular translocation of protein kinase C (PKC) from the soluble to the membranous fraction has been shown previously to correlate with biological activity of phorbol esters in several systems. In this paper, we describe that PKC translocation was a general phenomenon in all PKC containing cell types when fi...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-12-01 00:00:00
abstract::TER286 is a latent drug activated by human glutathione S-transferase (GST) isoforms P1-1 and A1-1 to produce a nitrogen mustard alkylating agent. M7609 human colon carcinoma, selected for resistance to doxorubicin, and MCF-7 human breast carcinoma, selected for resistance to cyclophosphamide, both showed increased sen...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-06-15 00:00:00
abstract::It has recently been reported that the human myeloma cell line U266 proceeds to undergo apoptosis after cultivation with the antiestrogen tamoxifen, thus raising the possibility that antiestrogens may be candidates for use in myeloma therapy. To obtain basic information on the effects of antiestrogens on myeloma cells...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
abstract::Since tumor suppressor gene DCC exhibits amino acid sequence homology to the neural cell adhesion molecule, there is a possibility that DCC might be related to tumor metastasis. In the present study, we examined 51 cases of primary esophageal carcinomas with regard to point mutations and loss of the DCC gene. We detec...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Previous work in our laboratory has indicated that free fatty acids stimulate synthesis of fibrinogen by the liver. The effect of the hypolipidemic agent clofibrate on hyperfibrinogenemia associated with tumors was evaluated by monitoring clofibrate-induced changes in plasma fibrinogen concentration and biosynthesis o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-10-01 00:00:00
abstract::We investigated the relationship between DNA cytosine methylation and the expression of two genes associated with resistance to DNA methylation damage. Variants of RajiMex- cells acquired resistance to N-methyl-N-nitrosourea by either reactivating a previously silent O6-methylguanine-DNA methyltransferase (MGMT) gene ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-06-15 00:00:00
abstract::Two human pancreatic cell lines, MIA PaCa 2 and Capan 2, were treated by photodynamic therapy in vitro with Photophrin (0.01-25 micrograms/ml; 24 h) and then light (1-50 J/cm2; lambda = 630 nm). The following model was fit to 6 datasets with weighted nonlinear regression: [sequence: see text] The symbols are: E, cell ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-07-15 00:00:00
abstract::Progression of well differentiated rat mammary adenocarcinomas to very anaplastic phenotypes was found to correlate with a systematic and significant amplification of a mutant HRAS allele. Tumors with high amplification levels of this oncogene were analyzed by chromosomal in situ hybridization; in four of the cases th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-11-15 00:00:00
abstract::Monoclonal antibodies (Mabs) against human ovarian mucinous and serous carcinoma were obtained by the Mab technique. Their reactivities against human tumors were tested by indirect immunofluorescence. One of the Mabs, named 4C7, derived from the spleen cells of mice immunized with mucinous carcinoma line OVA-1, reacte...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine nonmelanoma skin cancer, which is associated with the Merkel cell polyoma virus (MCPyV). Recently, expression of the terminal deoxynucleotidyl transferase (TdT) and the paired box gene 5 (PAX 5) has been consistently reported in the majority of MCCs. We ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0616
更新日期:2013-08-15 00:00:00
abstract::We have developed a model system which can be utilized for characterizing both the molecular basis of natural killer (NK):tumor interactions and the consequences of these interactions on tumor growth in vivo. This model system consists of several tumor lines which were derived from the murine lymphoma ASL1w under cond...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscur...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-2418
更新日期:2013-02-01 00:00:00
abstract::Expression of B7.1 costimulatory molecules on tumor cells has been shown to elicit antitumor immunity in mice. In the present study, we have developed a human B7.1 retroviral vector system to effectively transduce human melanoma cell lines and investigated the potential role of B7.1 in the generation of tumor-specific...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-04-15 00:00:00
abstract::Cancer chemotherapy may be improved by increasing antineoplastic drug specificity for tumor cells. We have synthesized a glucuronide prodrug that can be enzymatically converted to an antineoplastic agent at tumor cells that are able to bind beta-glucuronidase-monoclonal antibody conjugates. The glucuronide prodrug BHA...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-08-15 00:00:00