Claims
- 1. A method of decreasing the motility of an αvβ3 integrin expressing cell comprising cross-linking at least two αvβ3 integrins on said integrin expressing cells thereby inhibiting the motility of said cells.
- 2. The method of claim 1, wherein the integrins are cross linked by a homodimeric disintegrin.
- 3. The method of claim 2, wherein the homodimeric disintegrin is contortrostatin.
- 4. The method of claim 1, wherein the crosslinking disrupts FAK signaling.
- 5. The method of claim 1, wherein the crosslinking activates tyrosine phosphorylation of FAK.
- 6. The method of claim 1, wherein the crosslinking activates tyrosine phosphorylation of CAS.
- 7. The method of claim 1, wherein the crosslinking induces an alteration in cell morphology.
- 8. The method of claim 7, wherein the alteration changes cytoskeletal or focal adhesion structures.
- 9. The method of claim wherein the αvβ3 integrin expressing cell is a tumor cell.
- 10. A method of inhibiting the adhesion of integrin expressing cells to vitronectin comprising exposing said cells to contortrostatin so that contortrostatin binds to the integrin.
- 11. The method of claim 10, wherein said integrin is αvβ3 or αvβ5.
- 12. A homodimeric disintegrin comprising an amino acid sequence which is at least 90% percent identical to amino acid numbers 419 to 483 of SEQ ID NO: 2, wherein said contortrostatin amino acid sequence (i) binds to integrin αvβ5 and (ii) induces αvβ3-mediated tyrosine phosphorylation of CAS and FAK in tumor cells.
- 13. The homodimeric disintegrin of claim 12 having an amino acid sequence selected from the group consisting of:
(a) amino acid numbers 419 to 483 of SEQ ID NO: 2; (b) an amino acid sequence at least 95% identical to (a) as determined by FASTA or BLAST using default opening and gap penalties and a default scoring matrix.
- 14. A pharmaceutically acceptable composition comprising a pharmaceutically acceptable carrier and a homodimeric disintegrin according to claim 12.
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No. 09/460,295 filed Dec. 10, 1999, which is a continuation-in-part of U.S. Ser. No. 09/163,047, filed Sep. 29, 1998, which is a continuation-in-part of U.S. Ser. No. 08/745,603, filed Nov. 8, 1996, which issued as U.S. Pat. No. 5,814,609 on Sep. 29, 1998, which is a continuation-in-part of U.S. Ser. No. 08/632,691, filed Apr. 15, 1996, which issued as U.S. Pat. No. 5,731,288 on Mar. 24, 1998, which is a division of application Ser. No. 08/540,423, filed Oct. 10, 1995, now abandoned, which is a continuation of application Ser. No. 08/141,321 filed Oct. 22, 1993, now abandoned, which are all incorporated herein by reference.
Divisions (1)
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08540423 |
Oct 1995 |
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08632691 |
Apr 1996 |
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Continuations (2)
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08141321 |
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Continuation in Parts (4)
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09460295 |
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09460295 |
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08745603 |
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09163047 |
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08632691 |
Apr 1996 |
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08745603 |
Nov 1996 |
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