Abstract
Vascular proteins expressed at liver metastasis sites could serve as prognostic markers or as targets for pharmacodelivery applications. We employed a proteomic approach to define such proteins in three syngeneic mouse models of liver metastasis. Vascular structures were biotinylated in vivo by a terminal perfusion technique, followed by mass spectrometric analysis of accessible biotinylated proteins. In this manner, we identified 12 proteins for which expression was selectively associated with liver metastasis, confirming this association by tissue immunofluorescence or in vivo localization with radiolabeled antibodies. In summary, our findings identify vascular proteins that may have prognostic or drug-targeting use in addressing liver metastases, a common issue in many advanced cancers.
Highlights
IntroductionA promising approach to cancer therapy uses monoclonal antibody derivatives for the selective delivery of bioactive agents (e.g., full immunoglobulins for Fc-mediated cell killing, drugs with cleavable linkers, radionuclides, photosensitizers, procoagulant factors, and cytokines) to the tumor environment, sparing normal tissues [1,2,3,4,5,6,7,8]
A promising approach to cancer therapy uses monoclonal antibody derivatives for the selective delivery of bioactive agents to the tumor environment, sparing normal tissues [1,2,3,4,5,6,7,8]
We report the results of a perfusion-based chemical proteomics study performed on three different syngeneic mouse models of liver metastasis
Summary
A promising approach to cancer therapy uses monoclonal antibody derivatives for the selective delivery of bioactive agents (e.g., full immunoglobulins for Fc-mediated cell killing, drugs with cleavable linkers, radionuclides, photosensitizers, procoagulant factors, and cytokines) to the tumor environment, sparing normal tissues [1,2,3,4,5,6,7,8]. Distant site metastasis is the leading cause of cancer-associated mortality [9], the identification of selective and accessible markers of tumor metastasis represents an essential requirement for the development of antibody-based pharmacodelivery strategies capable of targeting disseminated lesions [10]. Ligand-mediated pharmacodelivery options are attractive in consideration of the fact that many conventional cytotoxic agents and therapeutic proteins typically exhibit a reduced uptake at the tumor site compared with normal organs [11, 12]. Biotinylated proteins can be efficiently recovered from normal tissues and pathologic specimens (e.g., tumors) by lysis in the presence
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
