Changes in BAI1 and nestin expression are prognostic indicators for survival and metastases in breast cancer and provide opportunities for dual targeted therapies.
The 2-year survival rate of patients with breast cancer brain metastases is less than 2%. Treatment options for breast cancer brain metastases are limited, and there is an unmet need to identify novel therapies for this disease. Brain angiogenesis inhibitor 1 (BAI1) is a GPCR involved in tumor angiogenesis, invasion, phagocytosis, and synaptogenesis. For the first time, we identify that BAI1 expression is significantly reduced in breast cancer and higher expression is associated with better patient survival. Nestin is an intermediate filament whose expression is upregulated in several cancers. We found that higher Nestin expression significantly correlated with breast cancer lung and brain metastases, suggesting both BAI1 and Nestin can be therapeutic targets for this disease. Here, we demonstrate the ability of an oncolytic virus, 34.5ENVE, to target and kill high Nestin-expressing cells and deliver Vstat120 (extracellular fragment of BAI1). Finally, we created two orthotopic immune-competent murine models of breast cancer brain metastases and demonstrated 34.5ENVE extended the survival of immune-competent mice bearing intracranial breast cancer tumors.
Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Walter Hans
WH
Meisen
Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Samuel
S
Dubin
Department of Radiation Oncology, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Steven T
ST
Sizemore
Department of Molecular and Cellular Biochemistry, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Haritha
H
Mathsyaraja
Department of Molecular and Cellular Biochemistry, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Katie
K
Thies
Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio. Department of Pathology, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Norman L
NL
Lehman
Small Animal Imaging Shared Resources, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio. Department of Biomedical Informatics, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Peter
P
Boyer
Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Alena Cristina
AC
Jaime-Ramirez
Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
J Bradley
JB
Elder
Small Animal Imaging Shared Resources, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio. Department of Biomedical Informatics, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Kimerly
K
Powell
Department of Radiation Oncology, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Arnab
A
Chakravarti
Department of Molecular and Cellular Biochemistry, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
Michael C
MC
Ostrowski
Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio. Department of Radiation Oncology, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio. balveen.kaur@osumc.edu.
Balveen
B
Kaur
D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009362:Neoplasm Metastasis; D064231:Nestin / Q000378:metabolism*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled; D014709:Vero Cells
C468226:ADGRB1 protein, human; D042501:Angiogenic Proteins; D014408:Biomarkers, Tumor; C577484:NES protein, human; D064231:Nestin; D043562:Receptors, G-Protein-Coupled