Sasha R Douglas1, Kay T Yeung2, Jing Yang3, Sarah L Blair4, Olga Cohen1, Brian P Eliceiri5. 1. Department of Surgery, University of California San Diego, La Jolla, California. 2. Department of Medicine, Division of Hematology and Oncology, University of California San Diego, La Jolla, California. 3. Department of Pharmacology, Moores Cancer Center, University of California San Diego, California. 4. Division of Breast Surgery and The Comprehensive Breast Health Center, University of California San Diego, La Jolla, California. 5. Department of Surgery, University of California San Diego, La Jolla, California. Electronic address: beliceiri@health.ucsd.edu.
Abstract
BACKGROUND: Extracellular vehicles (EVs) released by malignant tumor cells can mediate the immune response and promote metastasis through intercellular communication. EV analysis is an emerging cancer surveillance tool with advantages over traditional liquid biopsy methods. The aim of this pilot study is to identify actionable EV signatures in metastatic breast cancer. MATERIALS AND METHODS: Under an IRB-approved protocol for the analysis of patient plasma, samples were collected from women with newly diagnosed or progressive metastatic breast cancer and from women without cancer. Enriched EVs were analyzed via a bead-based multiplex assay designed to detect 37 distinct tumor-relevant epitopes. The mean fluorescent intensity of EV epitopes meeting a minimum threshold of detectability was compared between groups via independent samples t-test. Subgroup analysis was conducted for metastatic breast cancer patients who were positive for estrogen and/or progesterone receptors and negative for HER2. Other variables potentially affecting CD105 levels were also analyzed. RESULTS: CD105 was found to have a significantly higher mean fluorescent intensity in participants with metastatic breast cancer compared to control participants (P = 0.04). ER/PR+ subgroup analysis revealed a similar pattern compared to control participants (P = 0.01). Other analyzed variables were not found to have a significant correlation with CD105 levels. CONCLUSIONS: CD105 EV levels were significantly higher in samples from participants with breast cancer compared to controls. Given that CD105 is known to mediate angiogenesis and promote metastasis, EV-associated CD105 in plasma represents a potential biomarker for diagnosis, surveillance and therapeutic targeting in patients with metastatic breast cancer.
BACKGROUND: Extracellular vehicles (EVs) released by malignant tumor cells can mediate the immune response and promote metastasis through intercellular communication. EV analysis is an emerging cancer surveillance tool with advantages over traditional liquid biopsy methods. The aim of this pilot study is to identify actionable EV signatures in metastatic breast cancer. MATERIALS AND METHODS: Under an IRB-approved protocol for the analysis of patient plasma, samples were collected from women with newly diagnosed or progressive metastatic breast cancer and from women without cancer. Enriched EVs were analyzed via a bead-based multiplex assay designed to detect 37 distinct tumor-relevant epitopes. The mean fluorescent intensity of EV epitopes meeting a minimum threshold of detectability was compared between groups via independent samples t-test. Subgroup analysis was conducted for metastatic breast cancer patients who were positive for estrogen and/or progesterone receptors and negative for HER2. Other variables potentially affecting CD105 levels were also analyzed. RESULTS: CD105 was found to have a significantly higher mean fluorescent intensity in participants with metastatic breast cancer compared to control participants (P = 0.04). ER/PR+ subgroup analysis revealed a similar pattern compared to control participants (P = 0.01). Other analyzed variables were not found to have a significant correlation with CD105 levels. CONCLUSIONS: CD105 EV levels were significantly higher in samples from participants with breast cancer compared to controls. Given that CD105 is known to mediate angiogenesis and promote metastasis, EV-associated CD105 in plasma represents a potential biomarker for diagnosis, surveillance and therapeutic targeting in patients with metastatic breast cancer.
Authors: Cristina Grange; Marta Tapparo; Federica Collino; Loriana Vitillo; Christian Damasco; Maria Chiara Deregibus; Ciro Tetta; Benedetta Bussolati; Giovanni Camussi Journal: Cancer Res Date: 2011-06-13 Impact factor: 12.701
Authors: Daniela Osti; Massimiliano Del Bene; Germana Rappa; Mark Santos; Vittoria Matafora; Cristina Richichi; Stefania Faletti; Galina V Beznoussenko; Alexandre Mironov; Angela Bachi; Lorenzo Fornasari; Daniele Bongetta; Paolo Gaetani; Francesco DiMeco; Aurelio Lorico; Giuliana Pelicci Journal: Clin Cancer Res Date: 2018-10-04 Impact factor: 12.531