Endothelial Cell Expression of Testican mRNA

Marr, Henry S.; BaSalamah, Mohammad A.; Edgell, Cora‐Jean S.

doi:10.3109/10623329709053399

Cited by 26 publications

(23 citation statements)

References 23 publications

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“…The EAHy926 endothelial cell line (Marr et al, 1997) was the kind gift of Dr. Cora-Jean S. Edgell (Department of Pathology, University of North Carolina, Chapel Hill, NC). Cells were cultured as above plus 1ϫ hypoxanthine/aminopterin/thymidine.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Protein Kinase c-Src Reduces the Incidence of Breast Cancer Metastases and Increases Survival in Mice: Implications for Therapy

Rucci

Recchia

Angelucci

et al. 2006

J Pharmacol Exp Ther

125

102

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c-Src is a proto-oncogene, belonging to the nonreceptor protein kinases family, which plays a prominent role in carcinogenesis. In this study, we tested the hypothesis that c-Src could promote breast cancer metastasis acting on several cell types and that pharmacological disruption of its kinase activity could be beneficial for the treatment of metastases. Female BALB/cnu/nu mice were subjected to intracardiac injection of the human breast cancer cells MDA-MB-231 (MDA-231), which induced prominent bone and visceral metastases. of a c-Src kinase-dead dominant-negative construct (MDA-231-Src DN ) resulted in reduced morbidity, lethality, and incidence of metastases similar to the mice treated with the inhibitor. An analogous beneficial effect of c-Src inhibition was observed in subcutaneous and intratibial implanted tumors. In vitro, c-Src suppression reduced MDA-231 cell aggressiveness. It also impaired osteoclast bone resorption both directly and by reducing expression by osteoblasts of the osteoclastogenic cytokines interleukin-1␤ and interleukin-6, whereas parathyroid hormone-related peptide was not implicated. c-Src was also modestly but consistently involved in the enhancement of endothelial cell proliferation in vitro and angiogenesis in vivo. In conclusion, we propose that c-Src disruption affects the metastatic process and thus is a therapeutic target for the treatment of breast cancer.Breast cancer is a relatively common tumor, with an estimated incidence of 1.2 million new cases diagnosed worldwide every year (Henderson et al., 1993). The outcome of patients mainly depends on the development of distant metastases (Greenberg et al., 1996). Bone is the principal metastatic site in patients with mammary carcinomas (James et al., 2003), of whom approximately 20% survives for more than 5 years, whereas those with minor metastases in the bone can survive up to 10 years or more. In contrast, visceral metastases, although less common, are more likely to be fatal with a higher risk of early death.Consistent evidence suggests the involvement of the protooncogene c-Src in the development and progression of many human cancers, including breast carcinomas (Otthenoff-Kalff et This work was supported by the E.C. Grant METABRE (LSHM-CT-2003-503049) and by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC).Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

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Section: Methodsmentioning

confidence: 99%

Inhibition of Protein Kinase c-Src Reduces the Incidence of Breast Cancer Metastases and Increases Survival in Mice: Implications for Therapy

Rucci

Recchia

Angelucci

et al. 2006

J Pharmacol Exp Ther

125

102

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“…Similarly, in muscle development testican-1 becomes clustered at the neuromuscular junctions during postsynaptic differentiation (35). In man, testican-1 is expressed by neurons and by endothelial cells of a variety of tissues (36). An unstable 130-kDa form is present in blood and converted to a smaller stable form by unidentified plasma serine proteases (37).…”

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confidence: 99%

Characterization of SMOC-1, a Novel Modular Calcium-binding Protein in Basement Membranes

Vannahme¹,

Smyth²,

Miosge³

et al. 2002

Journal of Biological Chemistry

103

113

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We have isolated the novel gene SMOC-1 that encodes a secreted modular protein containing an EF-hand calcium-binding domain homologous to that in BM-40. It further consists of two thyroglobulin-like domains, a follistatin-like domain and a novel domain. Recombinant expression in human cells showed that SMOC-1 is a glycoprotein with a calcium-dependent conformation. Results from Northern blots, reverse transcriptase-PCR, and immunoblots revealed a widespread expression in many tissues. Immunofluorescence studies with an antiserum directed against recombinant human SMOC-1 demonstrated a basement membrane localization of the protein and additionally its presence in other extracellular matrices. Immunogold electron microscopy confirmed the localization of SMOC-1 within basement membranes in kidney and skeletal muscle as well as its expression in the zona pellucida surrounding the oocyte.

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“…Testican orthologs can be identified in other multicellular organisms such as Drosophila melanogaster and Caenorhabditis elegans, but not unicellular yeast, which may suggest an intercellular role for testican. The signal-like hydrophobic sequence encoded at the N-terminal of testican (2,4) supports the expectation that testican functions extracellularly.…”

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confidence: 56%

“…Testican is differentially expressed in human tissues. Its mRNA levels are highest in human brain, prostate, heart, testes, placenta, uterus, and kidney; levels are lower in other organs, and the mRNA is not detected in liver and lung (4,5). Thus, endothelial cells in some organs must express little or no testican mRNA.…”

mentioning

confidence: 99%

“…Testican cDNA clones related to the sequence of a peptide that had been purified as a proteoglycan from seminal plasma were identified in a testes cDNA library (1,2). Testican cDNA clones were independently identified by screening an endothelial cell library for sequences that are expressed by cultured human endothelial cells but not by certain other cell types (3,4). Testican is differentially expressed in human tissues.…”

mentioning

confidence: 99%

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