This new study was the first in which researchers evaluated the molecular repertoire of protein diversity in several patients, targeting multiple organs at once.
In three cancer patients, serial rounds of peptide collection were followed by biopsies from various tissues to determine where and how the peptides homed, which enabled the enrichment of targeting peptides for identifying ligand-receptors. After systemic delivery of a peptide library to the first patient, phage were recovered from organs, pooled and serially screened in two subsequent patients. Large-scale sequencing was then performed.
"This uncovered a new twist for the vascular map," Pasqualini said. "To this point, we had seen mainly addresses that were organ and tissue specific. Because of this synchronized method, we discovered some markers are vascular-associated at multiple sites."
Shared addresses surprise researchers
Analysis revealed four native ligand-receptors, three of which were previously unrecognized.
Two are shared among multiple tissues (integrin a4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white fat tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases).
The discovery of shared addresses especially intrigued researchers.
"No one knew about the novel aspect surrounding these particular proteins, and the fact that they can interact and come together to serve a common purpose," Pasqualini said. "There are likely to be many more."
A tissue-specific vascular-targeting system, comprising ANXA2 and prohibitin, was found as a ligand-receptor in human white adipo
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center