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 language | English |
|---|---|
| Pages (from-to) | 23186-23190 |
| Number of pages | 5 |
| Journal | Journal of Biological Chemistry |
| Volume | 268 |
| Issue number | 31 |
| Publication status | Published - 1993 |
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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 journal › Article
}
TY - JOUR
T1 - A conjugate between human urokinase and saporin, a type-1 ribosome- inactivating protein, is selectively cytotoxic to urokinase receptor- expressing cells
AU - Cavallaro, U.
AU - Del Vecchio, A.
AU - Lappi, D. A.
AU - Soria, M. R.
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0027371837&partnerID=8YFLogxK
M3 - Article
C2 - 8226837
AN - SCOPUS:0027371837
VL - 268
SP - 23186
EP - 23190
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 31
ER -