| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
5ß1 Integrin on Blood Vessels in Tumors
From the Department of Anatomy,* Cardiovascular Research Institute, Comprehensive Cancer Center, University of California, San Francisco; and Protein Design Labs, Incorporated, Fremont, California
Integrin 
5ß1 is among the proteins overexpressed on tumor vessels and is a potential target for diagnostics and therapeutics. Here, we mapped the distribution of 5ß1 integrin in three murine tumor models and identified sites of expression that are rapidly accessible to intravascular antibodies. When examined by conventional immunohistochemistry, 5ß1 integrin expression was strong on most blood vessels in RIP-Tag2 transgenic mouse tumors, adenomatous polyposis coli (apc) mouse adenomas, and implanted MCa-IV mammary carcinomas. Expression increased during malignant progression in RIP-Tag2 mice. However, immunoreactivity was also strong in normal pancreatic ducts, intestinal smooth muscle, and several other sites. To determine which sites of expression were rapidly accessible from the bloodstream, we intravenously injected anti-5ß1 integrin antibody and 10 minutes to 24 hours later examined the amount and distribution of labeling. The injected antibody strongly labeled tumor vessels at all time points but did not label most normal blood vessels or gain access to pancreatic ducts or intestinal smooth muscle. Intense vascular labeling by anti-5ß1 integrin antibody co-localized with the uniform CD31 immunoreactivity of tumor vessels and contrasted sharply with the patchy accumulation of nonspecific IgG at sites of leakage. This strategy of injecting antibodies revealed the uniform overexpression and rapid accessibility of 5ß1 integrin on tumor vessels and may prove useful in assessing other potential therapeutic targets in cancer.
This article has been cited by other articles:
 |
|
 |
|
  P. BALUK and D. M. MCDONALD Markers for Microscopic Imaging of Lymphangiogenesis and Angiogenesis Ann. N.Y. Acad. Sci., May 1, 2008; 1131(1): 1 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sawada, A. K. Mitra, A. R. Radjabi, V. Bhaskar, E. O. Kistner, M. Tretiakova, S. Jagadeeswaran, A. Montag, A. Becker, H. A. Kenny, et al. Loss of E-Cadherin Promotes Ovarian Cancer Metastasis via {alpha}5-Integrin, which Is a Therapeutic Target Cancer Res., April 1, 2008; 68(7): 2329 - 2339. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Seidler, S. Goldoni, C. Agnew, C. Cardi, M. L. Thakur, R. T. Owens, D. J. McQuillan, and R. V. Iozzo Decorin Protein Core Inhibits in Vivo Cancer Growth and Metabolism by Hindering Epidermal Growth Factor Receptor Function and Triggering Apoptosis via Caspase-3 Activation J. Biol. Chem., September 8, 2006; 281(36): 26408 - 26418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Umeda, S. Kachi, H. Akiyama, G. Zahn, D. Vossmeyer, R. Stragies, and P. A. Campochiaro Suppression and Regression of Choroidal Neovascularization by Systemic Administration of an {alpha}5beta1 Integrin Antagonist Mol. Pharmacol., June 1, 2006; 69(6): 1820 - 1828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. Yao, M. G. Ozawa, A. S. Varner, I. M. Kasman, Y. H. Chanthery, R. Pasqualini, W. Arap, and D. M. McDonald Antiangiogenic therapy decreases integrin expression in normalized tumor blood vessels. Cancer Res., March 1, 2006; 66(5): 2639 - 2649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakahara, S. M. Norberg, D. R. Shalinsky, D. D. Hu-Lowe, and D. M. McDonald Effect of Inhibition of Vascular Endothelial Growth Factor Signaling on Distribution of Extravasated Antibodies in Tumors Cancer Res., February 1, 2006; 66(3): 1434 - 1445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. McDonald and P. Baluk Imaging of Angiogenesis in Inflamed Airways and Tumors: Newly Formed Blood Vessels Are Not Alike and May Be Wildly Abnormal: Parker B. Francis Lecture Chest, December 1, 2005; 128(6_suppl): 602S - 608S. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
