A conjugate between human urokinase and saporin, a type-1 ribosome- inactivating protein, is selectively cytotoxic to urokinase receptor- expressing cells

U. Cavallaro, A. Del Vecchio, D. A. Lappi, M. R. Soria

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Urokinase-type plasminogen activator (uPA) confers invasive potential to transformed cells. Cancer cells express high numbers of uPA receptors (uPARs), which concentrate uPA activity at the invasive edge of cancer cells and the tumor mass. We synthesized a conjugate between human uPA and saporin (SAP), a ribosome-inactivating protein produced by Saponaria officinalis. Results of cell-killing assays showed that uPA is very effective at targeting saporin specifically to uPAR-expressing cells, whereas cell lines devoid of uPARs were not affected by the conjugate. Receptor-bound uPA is internalized only upon formation of a complex with one of its inhibitors (PAIs). However, our conjugate was highly cytotoxic even when the interaction between uPA and PAIs was prevented. Moreover, the α2-macroglobulin receptor, which has been reported to mediate the internalization of uPA·PAI complexes, seems not to be involved in cell killing caused by the uPA·SAP conjugate. Thus, uPA·SAP might follow a mechanism of internalization different from that of unconjugated uPA complexed to PAIs, although still uPAR-mediated. Our results also suggest that α2-macroglobulin and/or its receptor could mediate the internalization and cytotoxicity of unconjugated saporin, as it has been shown for other toxins.

Original languageEnglish
Pages (from-to)23186-23190
Number of pages5
JournalJournal of Biological Chemistry
Volume268
Issue number31
Publication statusPublished - 1993

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Type 1 Ribosome Inactivating Proteins
Urokinase-Type Plasminogen Activator
Polyamideimides
Urokinase Plasminogen Activator Receptors
Cells
Macroglobulins
Saponaria
Ribosome Inactivating Proteins
Neoplasms
Cytotoxicity
saporin
Tumors
Assays
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

A conjugate between human urokinase and saporin, a type-1 ribosome- inactivating protein, is selectively cytotoxic to urokinase receptor- expressing cells. / Cavallaro, U.; Del Vecchio, A.; Lappi, D. A.; Soria, M. R.

In: Journal of Biological Chemistry, Vol. 268, No. 31, 1993, p. 23186-23190.

Research output: Contribution to journalArticle

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T1 - A conjugate between human urokinase and saporin, a type-1 ribosome- inactivating protein, is selectively cytotoxic to urokinase receptor- expressing cells

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AU - Del Vecchio, A.

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AU - Soria, M. R.

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