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Titolo:
EXPRESSION OF PLASMINOGEN ACTIVATORS AND PLASMINOGEN-ACTIVATOR INHIBITORS IN CUTANEOUS MELANOMAS OF TRANSGENIC MELANOMA-SUSCEPTIBLE MICE
Autore:
DEVRIES TJ; KITSON JL; SILVERS WK; MINTZ B;
Indirizzi:
FOX CHASE CANC CTR,INST CANC RES,7701 BURHOLME AVE PHILADELPHIA PA 19111 FOX CHASE CANC CTR,INST CANC RES PHILADELPHIA PA 19111
Titolo Testata:
Cancer research
fascicolo: 20, volume: 55, anno: 1995,
pagine: 4681 - 4687
SICI:
0008-5472(1995)55:20<4681:EOPAAP>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
MIGRATING ENDOTHELIAL-CELLS; MALIGNANT SKIN MELANOMA; UROKINASE-TYPE; MOUSE; GENE; INVIVO; ANGIOGENESIS; DEGRADATION; MODULATION; INVASION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
T.J. Devries et al., "EXPRESSION OF PLASMINOGEN ACTIVATORS AND PLASMINOGEN-ACTIVATOR INHIBITORS IN CUTANEOUS MELANOMAS OF TRANSGENIC MELANOMA-SUSCEPTIBLE MICE", Cancer research, 55(20), 1995, pp. 4681-4687

Abstract

The Tyr-SV40E transgenic mouse model of malignant skin melanoma has been used here to generate melanomas in genetically identical (C57BL/6)mice for analysis of the plasminogen activator (PA) system during tumor development and progression. Twenty-two melanocytic lesions were examined by in situ zymography for PA activity and by immunohistochemistry for concomitant visualization of PA proteins; these lesions encompassed 3 nevi and 19 primary melanomas ranging from melanotic through mixed tumors to amelanotic tumors. Although urokinase-type plasminogen activator (u-PA) activity was not detected at premalignant stages, it began to appear early in tumorigenesis and became more prominent in later stages of a majority of the tumors, The activity was largely attributable to the endothelium of sprouting capillaries and to a lesser degree to granulocytes, fibroblastic cells, and occasional melanoma cellswithin tumors. Tissue-type plasminogen activator (t-PA) was undetectable or low in all cases. Of the PA inhibitors (PAI), PAI-1 was seen inendothelial and fibroblastic cells and in the extracellular matrix, whereas PAI-2 occurred in only one case and was melanoma cell associated, Eleven additional melanomas were analyzed by reverse transcription-PCR for PA expression in RNA extracts from relatively large tumor samples. These were obtained from eight primary melanomas and three metastases, again spanning melanotic, mixed, and amelanotic cases, From fourof the mixed primary tumors with distinct melanotic and amelanotic zones, the respective components were propagated separately in transgenic hosts as s.c. transplants to obtain data for clearly identifiable melanotic versus amelanotic parts, u-PA and PAI-1 mRNAs were expressed in all, t-PA expression varied greatly and was notably high in several amelanotic tumors or tumor components, possibly as a result of large blood vessels, as such vessels were seen to be t-PA positive in normal tissue. The u-PA activity in sprouting capillaries may indicate a rolein neoangiogenesis. Therefore, according to these mouse models, u-PA may indirectly be a potential therapeutic target against melanoma progression.

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Documento generato il 04/12/20 alle ore 19:44:51