Keywords

Breast Cancer, Extracellular Vesicles, CCT

Subject Categories

Cancer Biology | Cell Biology

Abstract

Detecting early metastatic progression or recurrence after initial treatment remains a major challenge in breast cancer (BCa). Current liquid biopsy approaches, including the detection of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), provide valuable information but are limited by analytical complexity and the lack of clinically actionable biomarkers. Native or naïve extracellular vesicles (EVs) have emerged as a promising alternative for liquid biopsy, as these particles are actively shed from tumor cells and carry molecular cargo that reflects their cells of origin. However, few studies have identified oncogenic EV-associated biomarkers. In this study, we focus on the eight-subunit protein-folding complex, Chaperonin-Containing TCP-1 (CCT), specifically its CCT2 subunit, which our lab identified as a key driver of cancer cell survival and invasiveness, as well as a biomarker for CTCs. Using an optimized EV isolation protocol coupled with a novel intra-vesicle flow cytometry method, we examined the CCT2 content of EVs derived from BCa cells. We demonstrate that BCa cells with elevated CCT2 expression, including some triple-negative breast cancer cell lines and cells engineered to exogenously express FLAG-tagged CCT2, release EVs enriched in both CCT2 protein and RNA compared with EVs from cells with lower CCT2 levels. Analysis of plasma and peripheral blood mononuclear cells (PBMCs) from BCa patients across stages and disease further revealed increased levels of CCT2-positive EVs and cells compared with healthy controls. Notably, a substantial fraction of CCT2-positive EVs lacked canonical EV markers such as CD63 or Alix, suggesting the presence of previously unrecognized, potentially oncogenic, EV subsets. Collectively, these findings identify CCT2 as a possible biomarker for tumor-derived EVs and demonstrate its utility for non-invasive monitoring of disease status. Tracking CCT2 levels in EVs may be a novel strategy for detecting early recurrence and assessing treatment responses in BCa patients.

Completion Date

2026

Semester

Summer

Committee Chair

Khaled, Annette

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Biotechnology MS

Format

PDF

Document Type

Thesis

Language

English

Release Date

8-15-2028

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Available for download on Tuesday, August 15, 2028

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