RESUMO
Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow cytometry screen on patient-derived glioblastoma (GBM) cells and identified junctional adhesion molecule A (JAM-A) as a CSC adhesion mechanism essential for self-renewal and tumor growth. JAM-A was dispensable for normal neural stem/progenitor cell (NPC) function, and JAM-A expression was reduced in normal brain versus GBM. Targeting JAM-A compromised the self-renewal of CSCs. JAM-A expression negatively correlated to GBM patient prognosis. Our results demonstrate that GBM-targeting strategies can be identified through screening adhesion receptors and JAM-A represents a mechanism for niche-driven CSC maintenance.
Assuntos
Moléculas de Adesão Celular/metabolismo , Células-Tronco Neoplásicas/metabolismo , Receptores de Superfície Celular/metabolismo , Nicho de Células-Tronco , Animais , Adesão Celular , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Citometria de Fluxo , Glioblastoma/metabolismo , Glioblastoma/patologia , Ensaios de Triagem em Larga Escala , Humanos , Camundongos , Células-Tronco Neoplásicas/fisiologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/fisiologia , Receptores de Superfície Celular/genéticaRESUMO
Colon cancer is a deadly disease affecting millions of people worldwide. Current treatment challenges include management of disease burden as well as improvements in detection and targeting of tumor cells. To identify disease state-specific surface antigen signatures, we combined fluorescent cell barcoding with high-throughput flow cytometric profiling of primary and metastatic colon cancer lines (SW480, SW620, and HCT116). Our multiplexed technique offers improvements over conventional methods by permitting the simultaneous and rapid screening of cancer cells with reduced effort and cost. The method uses a protein-level analysis with commercially available antibodies on live cells with intact epitopes to detect potential tumor-specific targets that can be further investigated for their clinical utility. Multiplexed antibody arrays can easily be applied to other tumor types or pathologies for discovery-based approaches to target identification.