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  • 1
    ISSN: 1573-7217
    Keywords: glycoprotein ; invasion ; malignancy marker ; membrane ; metastasis ; protease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Metastasizing cancer cells can invade the extracellular matrix using plasma membrane protrusions, termed invadopodia, that contact and dissolve the matrix. Various membrane associated proteases localized on the invadopodial membranes are responsible for the extracellular matrix degradation. Work from our laboratory shows that secreted proteases including Gelatinase A, and high molecular weight integral membrane proteases are associated with cell surface invadopodia. Three cell types, including chicken embryonic cells transformed by Rous sarcoma virus, human malignant melanoma cell line LOX, and human breast carcinoma cell line MDA-MB-231, retain the invasive phenotypein vitro, express invadopodia, degrade and enter into a fibronectin-rich collagenous matrix. We suggest that invadopodium-associated proteases are ideal targets for the diagnosis and treatment of cancer as their presence in association with primary tumors may signal increased metastatic potential. An approach toward the development of new prognostic markers for breast malignancy involved production of monoclonal antibodies directed against membrane proteases in a mixture of glycoproteins. Double immunofluorescent technique using a known invadopodium marker is designed to select specific monoclonal antibodies colocalizing at the invasion front, on invadopodia of cancer cells. Membrane protease accessibility at the cell surface can therefore be exploited for therapeutic advances by the development of specific antibodies and inhibitors that block their activities, and by the use of monoclonal antibodies to target cytotoxic molecules to micrometastases. Also, this same accessibility may potentially be used to detect surface proteases on micrometastases or to detect components shed by micrometastases in serum.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer and metastasis reviews 11 (1992), S. 389-409 
    ISSN: 1573-7233
    Keywords: 12(S)-HETE ; 13(S)-HODE ; TXA2 ; PGI2 ; platelet ; vessel wall ; metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prostaglandins and other eicosanoids have been studied extensively in their physical, biochemical, biophysical and pharmacological aspects. However, studies on their role in tumor progression, especially metastases are relatively recent. Following a brief overview of the history of discovery and metabolism of eicosanoids and other fatty acids, we discuss the functions of these fatty acids (with emphasis on prostacyclin, thromboxane A2, 12-hydroxyeicosatetraenoic acid and 13-hydroxyoctadecadienoic acid) in cell transformation, tumor promotion and particularly in tumor cell metastasis. The relation between these monohydroxy fatty acids and tumor cell metastasis is discussed from three different perspectives, i.e., their effects on tumor cells, on platelets and on endothelial cells. The mechanism of these effects are then addressed at cell adhesion molecule, motility, protease, cell cytoskeleton, protein kinase and eicosanoid receptor levels. Finally, regulation of three key enzymes which generate eicosanoids (phospholipase, prostaglandin endoperoxide synthase and lipoxygenase) is explored.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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