EXPANSION AND CHARACTERIZATION OF HUMAN BREAST CIRCULATING CANCER CELLS

Abstract

CIRCULATING TUMOR CELLS (CTCS) ARE HETEROGENEOUS CANCER CELLS IN THE PERIPHERAL BLOODSTREAM WHICH MAY PARTICIPATE IN THE PROCESS OF METASTASIS. THIS STUDY PRESENTS A MICROWELL-BASED TECHNIQUE FOR THE CULTURE OF CTCS (WITH MINIMAL PERSISTING BLOOD CELLS) FROM PATIENTS. THE PROTOCOL ALLOWED ENRICHMENT OF A WIDE RANGE OF HETEROGENEOUS CANCER CELLS, LEADING TO A HIGH DETECTION EFFICIENCY (62.2%, N=391). CHARACTERIZATION OF THE CULTURES REVEALED CELLULAR HETEROGENEITY VIA HISTOLOGICAL STAINING, PROTEIN AND GENE EXPRESSION ANALYSES. CULTURED CTCS PRESENTED A RANGE OF EPITHELIAL?MESENCHYMAL TRANSITION (EMT) PHENOTYPES, INCLUDING THOSE THAT EXPRESSED MARKERS CORRELATING TO BREAST CANCER STEM CELLS (CSC). THE ABILITY TO FORM CLUSTERS CORRELATED WITH PATIENT OVERALL SURVIVAL (OS), AND WAS REDUCED IN SAMPLES OBTAINED AT LATER TREATMENT TIME POINTS. OVERALL, THE MICROWELL CTC CULTURE ASSAY CAN POTENTIALLY SERVE AS A VALUABLE TOOL FOR RAPID MONITORING OF PATIENT PROGNOSIS, WHICH MAY ENABLE CTC PROF