This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, C. Articles by Edgington, T. S. Search for Related Content PubMed PubMed Citation Articles by Liu, C. Articles by Edgington, T. S.

Prostate-specific Membrane Antigen Directed Selective Thrombotic Infarction of Tumors¹

Department of Immunology, The Scripps Research Institute, La Jolla, California 92037 [C. L., H. H., A. E., T. S. E.]; Attenuon, LLC, San Diego, California 92121 [F. D.]; Applied Molecular Evolution, San Diego, California 92121 [C. D.]; Wayne State School of Medicine, Detroit, Michigan 48201 [R. S.]; and Department of Urology, University of Washington, Seattle, Washington 98185 [R. V.]

Prostate-specific membrane antigen (PSMA), a glutamyl preferring carboxypeptidase, is found in prostate and other carcinomas present on both tumor cells and associated microvascular lining cells. We find that the channel structures delineated by PSMA-expressing cells in human and rat prostate tumors are in functional continuity with the vasculature and thus form part of tumor microvasculature. The PSMA-positive cell-outlined channels are CD31 negative and mutually exclusive of CD31-positive cell-lined channels elsewhere in the tumor consistent with tumor cells adapted to a pseudoendothelial phenotype in vasculogenic mimicry. To assess the functional potential of such PSMA-lined microvasculature to selectively direct infarctive tumor therapy, we coupled the soluble extracellular domain of tissue factor to a PSMA catalytic site inhibitor to create a PSMA-directed selective tumor vascular thrombogen (STVT). This protein induced selective local in vivo infarctive necrosis of the rat Mat Lu prostate tumor when administered i.v. The combined administration of this STVT with low-dose doxorubicin produced a profound tumoricidal effect, resulting in complete eradication of some tumors. This is consistent with the therapeutic potential for a PSMA-directed STVT and expands the potential for selective infarctive ablation of tumors.

This article has been cited by other articles:

				X. Huang, W.-Q. Ding, J. L. Vaught, R. F. Wolf, J. H. Morrissey, R. G. Harrison, and S. E. Lind A soluble tissue factor-annexin V chimeric protein has both procoagulant and anticoagulant properties Blood, February 1, 2006; 107(3): 980 - 986. [Abstract] [Full Text] [PDF]

				W. Wu, Y. Luo, C. Sun, Y. Liu, P. Kuo, J. Varga, R. Xiang, R. Reisfeld, K. D. Janda, T. S. Edgington, et al. Targeting Cell-Impermeable Prodrug Activation to Tumor Microenvironment Eradicates Multiple Drug-Resistant Neoplasms Cancer Res., January 15, 2006; 66(2): 970 - 980. [Abstract] [Full Text] [PDF]

				H. Akiyama, K. A. Mohamedali, R. L. e Silva, S. Kachi, J. Shen, C. Hatara, N. Umeda, S. F. Hackett, S. Aslam, M. Krause, et al. Vascular Targeting of Ocular Neovascularization with a Vascular Endothelial Growth Factor121/Gelonin Chimeric Protein Mol. Pharmacol., December 1, 2005; 68(6): 1543 - 1550. [Abstract] [Full Text] [PDF]

				T. Kessler, R. Bieker, T. Padro, C. Schwoppe, T. Persigehl, C. Bremer, M. Kreuter, W. E. Berdel, and R. M. Mesters Inhibition of Tumor Growth by RGD Peptide-Directed Delivery of Truncated Tissue Factor to the Tumor Vasculature Clin. Cancer Res., September 1, 2005; 11(17): 6317 - 6324. [Abstract] [Full Text] [PDF]

				A. Dienst, A. Grunow, M. Unruh, B. Rabausch, J. E. Nor, J. W. U. Fries, and C. Gottstein Specific Occlusion of Murine and Human Tumor Vasculature by VCAM-1-Targeted Recombinant Fusion Proteins J Natl Cancer Inst, May 18, 2005; 97(10): 733 - 747. [Abstract] [Full Text] [PDF]

				C. Liu, C. Dickinson, J. Shobe, F. Donate, W. Ruf, and T. Edgington A hybrid fibronectin motif protein as an integrin targeting selective tumor vascular thrombogen Mol. Cancer Ther., July 1, 2004; 3(7): 793 - 801. [Abstract] [Full Text] [PDF]

				P. E. Thorpe Vascular Targeting Agents as Cancer Therapeutics Clin. Cancer Res., January 15, 2004; 10(2): 415 - 427. [Abstract] [Full Text] [PDF]

				J. S. Palumbo, K. E. Talmage, H. Liu, C. M. La Jeunesse, D. P. Witte, and J. L. Degen Plasminogen supports tumor growth through a fibrinogen-dependent mechanism linked to vascular patency Blood, October 15, 2003; 102(8): 2819 - 2827. [Abstract] [Full Text] [PDF]

				W. Ruf, E. A. Seftor, R. J. Petrovan, R. M. Weiss, L. M. Gruman, N. V. Margaryan, R. E. B. Seftor, Y. Miyagi, and M. J. C. Hendrix Differential Role of Tissue Factor Pathway Inhibitors 1 and 2 in Melanoma Vasculogenic Mimicry Cancer Res., September 1, 2003; 63(17): 5381 - 5389. [Abstract] [Full Text] [PDF]

				A. R. Hess, E. A. Seftor, R. E. B. Seftor, and M. J. C. Hendrix Phosphoinositide 3-Kinase Regulates Membrane Type 1-Matrix Metalloproteinase (MMP) and MMP-2 Activity during Melanoma Cell Vasculogenic Mimicry Cancer Res., August 15, 2003; 63(16): 4757 - 4762. [Abstract] [Full Text] [PDF]