title: Phosphatidylserine-selective targeting and anticancer effects of SapC-DOPS nanovesicles on brain tumors.
abstract: Brain tumors, either primary (e.g., glioblastoma multiforme) or secondary (metastatic), remain among the most intractable and fatal of all cancers. We have shown that nanovesicles consisting of Saposin C (SapC) and dioleylphosphatidylserine (DOPS) are able to effectively target and kill cancer cells both in vitro and in vivo. These actions are a consequence of the affinity of SapC-DOPS for phosphatidylserine, an acidic phospholipid abundantly present in the outer membrane of a variety of tumor cells and tumor-associated vasculature. In this study, we first characterize SapC-DOPS bioavailability and antitumor effects on human glioblastoma xenografts, and confirm SapC-DOPS specificity towards phosphatidylserine by showing that glioblastoma targeting is abrogated after in vivo exposure to lactadherin, which binds phosphatidylserine with high affinity. Second, we demonstrate that SapC-DOPS selectively targets brain metastases-forming cancer cells both in vitro, in co-cultures with human astrocytes, and in vivo, in mouse models of brain metastases derived from human breast or lung cancer cells. Third, we demonstrate that SapC-DOPS have cytotoxic activity against metastatic breast cancer cells in vitro, and prolong the survival of mice harboring brain metastases. Taken together, these results support the potential of SapC-DOPS for the diagnosis and therapy of primary and metastatic brain tumors.
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors: Víctor M
authors: VM
authors: Blanco
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Zhengtao
authors: Z
authors: Chu
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors: Subrahmanya D
authors: SD
authors: Vallabhapurapu
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors: Mahaboob K
authors: MK
authors: Sulaiman
authors: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors: Ady
authors: A
authors: Kendler
authors: Division of Hematology/Oncology, Georgia Regents University, GRU Cancer Center, Augusta, Georgia.
authors: Olivier
authors: O
authors: Rixe
authors: Department of Neurosurgery, University of Cincinnati Brain Tumor Center, and Mayfield Clinic, Cincinnati, Ohio.
authors: Ronald E
authors: RE
authors: Warnick
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors: Robert S
authors: RS
authors: Franco
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Xiaoyang
authors: X
authors: Qi
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D010718:Phosphatidylserines / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011897:Random Allocation; D049231:Saposins / Q000008:administration & dosage* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D010718:Phosphatidylserines; D049231:Saposins