The Tumor Associated Lectin Galectin‐3 Can Bind and Sequester Cancer Biomarkers

Abstract

Most covalently‐linked glycans of glycoprotein cancer biomarkers are potential binding epitopes of tumor‐associated endogenous lectin galectin‐3 (Gal‐3). As glycoprotein biomarkers and Gal‐3 could be secreted by the same tumor cells, they could exist in the same vicinity. We hypothesized that Gal‐3 and the respective biomarker could engage in high affinity binding due to their close proximity. Such binding could result in mutual sequestration through cross‐linked complex formation. We tested our hypothesis by using Thyroglobulin (Tg) and human Gal‐3. Tg, a thyroidal glycoprotein, is a pre‐ and postoperative biomarker of differentiated thyroid cancer (DTC) and Gal‐3 is secreted by malignant thyroid cells. We found that these two biomarkers, produced by thyroid cancer cells, interacted with each other with submicromolar affinity and formed insoluble cross‐linked complexes at their stoichiometric concentrations. One Tg molecule bound up to 14 molecules of Gal‐3. Such complex formation mutually locked both Tg and Gal‐3 in cross‐linked complexes, decreasing the concentration of their freely available forms in the solutions. Formation of the Tg–Gal‐3 complexes was reversible as preformed complexes were found to be sensitive to free Tg and free Gal‐3. Both free Tg and Gal‐3 individually dissolved preformed Tg–Gal‐3 complexes in a concentration‐dependent manner. Complex formation between Tg and Gal‐3 and the sensitivity of the complexes to free Tg and Gal‐3 can potentially influence their biological functions. Sequestration of Tg by Gal‐3 in cross‐linked complexes might also interfere with their clinical detection, the same way Tg autoantibody (TgAb) is reported to interfere in clinical Tg assays. The data presented here also support a model of Gal‐3‐mediated homeostasis of Tg. The present findings could be relevant to other cancers that produce glycoprotein biomarkers and Gal‐3 [1].Support or Funding InformationMichigan Technological University