New molecular sensor enables fluorescence imaging to assess sarcoma severity

Researchers at Korea University School of Medicine have identified a new candidate marker for determining sarcoma severity and metastasis and developed a molecular sensor that enables fluorescence imaging targeting this marker.

The advance was published as a cover story in Angewandte Chemie International Edition.

Sarcomas are a large group of cancers that develop in soft tissues. Due to their heterogeneous nature, it is difficult to quantitatively assess the severity and metastasis of sarcomas in clinical pathology, which complicates diagnosis and prognosis monitoring.

Moreover, conventional cancer stem cell (CSC) markers often exhibit overexpression in heterogeneous malignancies, complicating the identification and isolation of CSCs in tumor cells.

The research team, led by Professor Jun-Seok Lee (Department of Pharmacology) and Professor Woo Young Jang (Department of Orthopaedic Surgery), found a correlation between the expression of the conventional CSC marker (CD44) and the prostaglandin synthesis network. They found that the expression of cyclooxygenase (COX) showed statistical specificity in different sarcomas.

Based on these results, the researchers designed two fluorescent probes (BD-IMC-1, BD-IMC-2) that target COX enzymes and activate fluorescence upon disaggregation. This innovative approach enables the visualization of CSCs in sarcoma tissues.

Specifically, they linked fluorescent BODIPY molecules to the COX inhibitor indomethacin to design molecules that induce the self-aggregation of nanostructures and remain in a fluorescently quenched state in aqueous solutions. These molecules exhibit sensitive fluorescence only when bound to COX enzymes, functioning as chemosensors. By using COX inhibitors and fluorescent structures to disaggregate the fluorescent molecules, they designed an imaging sensor that turns on fluorescence.

In the process, they also identified novel candidate markers, suggesting the need for further systematic research into the correlation between COX expression and CSC expression in sarcoma tissues.

Previously, imaging molecules targeting COX enzymes induced changes in fluorescence characteristics at the single-molecule level to visualize COX enzymes. However, this study is the first to report imaging target proteins in fixed clinical samples based on the fluorescence characteristics of structural changes in fluorescent multicomplexes.

Professor Jun-Seok Lee from the Department of Pharmacology said, “The newly developed fluorescent molecular sensor does not rely on changes in fluorescence characteristics at the single molecule level, but utilizes the self-aggregated state and characteristics of multiple molecules, making it effective in complex samples such as biological tissues.”

He added: “This research represents a novel strategy for the development of imaging sensors for various biological targets, contributing to the development of imaging-based diagnostic and prognostic monitoring techniques for sarcoma.”

Provided by Korea University School of Medicine