Galectins in Cancer and the Microenvironment: Functional Roles, Therapeutic Developments, and Perspectives

Abstract

Changes in cell growth and metabolism are affected by the surrounding environmental factors to adapt to the cell’s most appropriate growth model. However, abnormal cell metabolism is correlated with the occurrence of many diseases and is accompanied by changes in galectin (Gal) performance. Gals were found to be some of the master regulators of cell–cell interactions that reconstruct the microenvironment, and disordered expression of Gals is associated with multiple human metabolic-related diseases including cancer development. Cancer cells can interact with surrounding cells through Gals to create more suitable conditions that promote cancer cell aggressiveness. In this review, we organize the current understanding of Gals in a systematic way to dissect Gals’ effect on human disease, including how Gals’ dysregulated expression affects the tumor microenvironment’s metabolism and elucidating the mechanisms involved in Gal-mediated diseases. This information may shed light on a more precise understanding of how Gals regulate cell biology and facilitate the development of more effective therapeutic strategies for cancer treatment by targeting the Gal family.

Glycan-Lectin Interactions as Novel Immunosuppression Drivers in Glioblastoma

“…S-type lectins, or galectins, are defined by the presence of at least one conserved carbohydrate recognition domain (CRD) with high affinity for lactose or N -acetyllactosamine (LacNAc; Galβ1-4GlcNAc)-containing ligands. Currently, galectins are structurally differentiated in three groups, as they can exist as dimeric form (galectin-1, -2, -5, -7, -10, -11, -13, -14, -15), tandem-repeat form (galectin-4, -6, -8, -9) and the monomer or multivalent chimera type (galectin-3) [ 130 ].…”

“…Galectins can be retained in the cytosol or secreted both by transformed and normal cells, such as fibroblasts, endothelial and immune cells [ 131 , 132 ]. Galectins are involved in a wide range of basic cellular functions, as apoptosis, proliferation, cell adhesion and signaling, but also in immune system modulation and cancer development [ 130 ]. Interestingly, galectins exert their function both intracellularly and extracellularly [ 133 ].…”

“…The abundant galectins levels both in TME and peripheral blood have been proposed as prognostic factors and associated to a negative prognosis for oncologic patients [ 130 , 136 ]. Several galectins have been found in both neurons and glial cells and physiologically contribute to CNS development and functions.…”

“…Galectin-3 and -8 role in GB progression is less well defined. Little is known about their immune-related functions, while a better knowledge on their interplay with ECM is available (see Table 2 ) [ 130 , 137 ]. Depending on its expression, galectin-3 is able to reinforce or weak cell adhesion and cell–matrix interactions promoting the activation of pathway involved in ECM remodeling and EMT [ 156 , 157 ].…”

New opportunities for immunomodulation of the tumour microenvironment using chemical tools

“…the application of glycoimmune checkpoint blockers or CLR agonists) has also emerged as a feasible option for modulating immune responses. 39,286–290…”