LA JOLLA, Calif. , June 20, 2002
|Erkki Ruoslahti, M.D., Ph.D.|
Researchers at the Burnham Institute have identified a molecular postal code for lymphatic vessels in malignant tumors. Dr. Erkki Ruoslahti and his coworkers discovered a peptide that specifically zeros in on the lymphatic vessels in malignant tumors. The peptide is taken up by cells that form the inner lining of lymphatic vessels in tumors and by the tumor cells, ultimately traveling inside the nuclei of these cells. The results show for the first time that the lymphatic vessels in tumors can carry a specific marker. It may be possible to use this peptide to forestall metastatic spreading of cancers through the lymphatic system.
A few years ago, Dr. Ruoslahti developed a new method for probing the differences that exist between tumor vessels and vessels in normal tissues. This method uses phage, a virus that infects bacteria, to reveal which peptides in a collection of billions of peptides bind to vessels in tumors, but not in normal tissues. The researchers have shown that tumor-homing peptides isolated in this manner can be used to target drugs into tumors, and that the targeting enhances the activity of the drugs and reduces their side effects.
The current study, published in the July 1st edition of Nature Medicine, describes a nine-amino acid peptide, named LyP-1, that homes specifically to lymphatic tissue in tumors. LyP-1’s homing to lymphatic vessels was confirmed by labeling the peptide with a fluorescent die: the labeled LyP-1 was detected in tissues co-localizing with three known markers for the lymphatic vessels. LyP-1 was not detected in tumor blood vessels, which Dr. Ruoslahti’s group has targeted with other peptides.
LyP-1 was first identified from a breast cancer tumor, but it also binds to the lymphatics and tumor cells in other kinds of tumors, including prostate cancer in mice. However, some tumors have been negative for LyP-1 binding. The group is searching for peptides that would recognize the lymphatics in these LyP-1-negative tumors.
The lymphatic vessels serve as a frequent route for cancer metastasis. Breast cancer and prostate cancer, in particular, spread to the regional lymph nodes through this route. Using LyP-1 to target drugs to tumors may provide the means of blocking this path to metastasis, while also destroying the tumor cells that are close to the lymphatics and therefore poised to metastasize.
The Burnham Institute has filed a patent on LyP-1 and hopes to license the invention to a company for further development.
Erkki Ruoslahti, M.D., Ph.D., is Distinguished Professor at the NCI-designated Cancer Center, The Burnham Institute in La Jolla, CA.
Co-authors on this paper: Pirjo Laakkonen, Ph.D., Cancer Research Center, The Burnham Institute; Kimmo Porkka, M.D., Ph.D., Helsinki University Central Hospital; Jason Hoffman, M.S., Ph.D. candidate, Program in Molecular Pathology, The Burnham Institute and Department of Pathology, University of California San Diego School of Medicine.
This study was supported by grants from the National Cancer Institute, the Susan G. Komen Breast Cancer Foundation, awarded to Dr. Erkki Ruoslahti; fellowships from the Academy of Finland and the Finnish Cultural Foundation awarded to Dr. Pirjo Laakkonen; and a National Cancer Institute Training Grant Fellowship in the Molecular Pathology of Cancer awarded to Jason Hoffman.