CXCL12-loaded-hydrogel (CLG): A new device for metastatic circulating tumor cells (CTCs) capturing and...

Area of Science:

• Oncology
• Biomaterials Science
• Cell Biology

Background:

• Circulating Tumor Cells (CTCs) are rare but critical drivers of metastasis.
• Developing effective methods to isolate and characterize CTCs with metastatic potential is essential for cancer research and treatment.
• The CXCL12-CXCR4 axis plays a role in cancer cell invasion and metastasis.

Purpose of the Study:

• To develop and evaluate a CXCL12-loaded hyaluronic-gel (CLG) for trapping and characterizing invasive circulating tumor cells (CTCs).
• To assess the efficiency of CLG in capturing CTCs from various cancer cell lines and patient blood samples.
• To compare the performance of CLG with conventional methods for CTC isolation.

Main Methods:

• Human cancer cell lines (HT29, A498, H460, OVCAR8) were cultured on empty gels (EG) or CLG.
• CLG-infiltrated cells were analyzed for invasion, migration, colony formation, and expression of CXCR4, E-Cadherin, and Vimentin.
• A clinical trial (TRAP4MET) evaluated CLG for CTC isolation from 48 patients with advanced cancers (OC, LC, GBM, EC, RCC).
• Patient peripheral blood mononuclear cells (PBMCs) were isolated and seeded on CLG for CTC enumeration using specific markers (DAPI+/CD45-/pan-CK+).

Main Results:

• Human cancer cells infiltrated CLG more efficiently than EG across all tested cell lines.
• CLG-recovered cells exhibited enhanced migratory and colony-forming capabilities, along with hybrid-mesenchymal features and increased CXCR4 expression.
• CLG successfully isolated CTCs in a high percentage of patients across multiple cancer types (OC, LC, CRC, EC, RCC, GBM).
• CLG isolated significantly higher numbers of CTCs compared to ScreenCell™ in ovarian cancer, lung cancer, and glioblastoma.

Conclusions:

• CLG is an effective tool for isolating invasive CTCs with metastatic potential.
• The CLG system demonstrates superior performance in capturing CTCs compared to conventional methods in specific cancer types.
• CLG offers a promising new approach for the detection and characterization of CTCs in cancers lacking reliable detection methods.