Journal article
Tissue factor as a novel diagnostic target for early detection of ovarian cancer using ultrasound microbubbles
Gynecologic oncology, Vol.173, pp.138-150
06/2023
DOI: 10.1016/j.ygyno.2023.04.008
PMID: 37178671
Abstract
Ovarian cancer (OC) is the deadliest gynecologic malignancy, with an overall 5-year survival rate of less than 30%. The existing paradigm for OC detection involves a serum marker, CA125, and ultrasound examination, neither of which is sufficiently specific for OC. This study addresses this deficiency through the use of a targeted ultrasound microbubble directed against tissue factor (TF).
TF expression was examined in both OC cell lines and patient-derived tumor samples via western blotting and IHC. In vivo microbubble ultrasound imaging was analyzed using high grade serous ovarian carcinoma orthotopic mouse models.
While TF expression has previously been described on angiogenic, tumor-associated vascular endothelial cells (VECs) of several tumor types, this is first study to show TF expression on both murine and patient-derived ovarian tumor-associated VECs. Biotinylated anti-TF antibody was conjugated to streptavidin-coated microbubbles and in vitro binding assays were performed to assess the binding efficacy of these agents. TF-targeted microbubbles successfully bound to TF-expressing OC cells, as well as an in vitro model of angiogenic endothelium. In vivo, these microbubbles bound to the tumor-associated VECs of a clinically relevant orthotopic OC mouse model.
Development of a TF-targeted microbubble capable of successfully detecting ovarian tumor neovasculature could have significant implications towards increasing the number of early-stage OC diagnoses. This preclinical study shows potential for translation to clinical use, which could ultimately help increase the number of early OC detections and decrease the mortality associated with this disease.
•Identified that Tissue factor (TF) is uniquely expressed in ovarian tumor vasculature.•Developed a novel TF-targeting ultrasound microbubble for detection of early-stage OC.•Validated this TF-targeted microbubble using a clinically relevant OC mouse models.
Details
- Title: Subtitle
- Tissue factor as a novel diagnostic target for early detection of ovarian cancer using ultrasound microbubbles
- Creators
- Meghan M. Newcomer - Case Western Reserve UniversityKalpana Deepa Priya Dorayappan - The Ohio State University Wexner Medical CenterVincent Wagner - The Ohio State University Wexner Medical CenterAdrian A. Suarez - The Ohio State University Wexner Medical CenterCorinne A. Calo - The Ohio State University Wexner Medical CenterEileen L. Kalmar - The Ohio State UniversityG. Larry Maxwell - Inova Health SystemDavid O’Malley - The Ohio State University Wexner Medical CenterDavid E. Cohn - The Ohio State University Wexner Medical CenterMichael F. Tweedle - The Ohio State UniversityKaruppaiyah Selvendiran - The Ohio State University Wexner Medical Center
- Resource Type
- Journal article
- Publication Details
- Gynecologic oncology, Vol.173, pp.138-150
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.ygyno.2023.04.008
- PMID
- 37178671
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Language
- English
- Date published
- 06/2023
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984459620202771
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