Galectins in the Tumor Microenvironment: Focus on Galectin-1

Abstract

In the last decades, the focus of cancer research has moved from epithelial cells to the tumor milieu, in an effort to better understand tumor development and progression, and with the important end goal of translating this knowledge into effective therapies.The galectin family of glycan-binding proteins displays important functions in cancer development and progression. Numerous groups have made outstanding contributions to deepen our knowledge about the role of galectins in the tumor-stroma crosstalk, defining them as key players in modulating interactions between tumor cells and the extracellular matrix, fibroblasts, endothelium, and the immune system. While several members of the family have been of particular interest until now, others are still considered as future exploding stars. This chapter provides an overview for galectin-1, the first identified and still one of the most well-studied galectins, and highlights the very important implications in its regulation of the tumor microenvironment in many different tumor types. Besides, a glimpse of the role of other galectins in the tumor milieu is also provided. Gaining a deeper understanding about the numerous roles of galectin-1 will not only help us to better understand other galectins but also is likely to result in the development of more effective cancer therapies.

Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression

“…It is known that Gal-1 lacks a specific signal sequence for secretion via the conventional pathway, which suggests the involvement of unconventional secretion pathways, such as secretory autophagy ( Martinez-Bosch and Navarro, 2020 ). To determine the secretory pathway of Gal-1 in MCM-treated macrophages, the autophagy inhibitor, 3-MA, and the classical secretion pathway inhibitor, brefeldin A (BFA), were used.…”

“…The upregulation of Gal-1 in HCC cells is considered the primary source of soluble Gal-1 in TME. Interestingly, emerging reports demonstrate that Gal-1 is also wildly expressed in cancer stromal cells, such as fibroblasts, endothelial cells, T cells, and macrophages ( Martinez-Bosch and Navarro, 2020 ). In response to stimuli from cancer cells or TME, stromal cell-derived Gal-1 can act with a paracrine effect to support cancer development.…”

“…Notably, overexpression of Gal-1 is linked to the promotion of many types of cancer progression. Gal-1 in TME has been revealed to support tumor growth by increasing cell adhesion, invasiveness, angiogenesis, and evasion of immune surveillance ( Goud et al, 2019 ; Martinez-Bosch and Navarro, 2020 ). Recent reports further explored that Gal-1 is essential for inducing the sorafenib and cisplatin resistance in HCC ( Su et al, 2016 ; Zhang et al, 2016 ).…”

Unraveling How Tumor-Derived Galectins Contribute to Anti-Cancer Immunity Failure

“…In particular, the production of galectins-1, -3, -7, -8, and -9 is deregulated during tumorigenesis [ 15 , 16 , 17 ]. These galectins are detected in transformed cells and their associated stroma in various types of cancers [ 18 , 19 ]. In the latter case, it is not clear whether stromal cells produce galectins by themselves or take them up from neighboring transformed cells [ 20 , 21 , 22 ].…”

Prevalence of serum galectin‑1 autoantibodies in seven types of cancer: A potential biomarker

“…Galectin-1, an endogenous lectin found at immune-privileged sites, has a critical role in the regulation of the immune response in the tumor microenvironment ( 1 ). Wide varieties of biological phenomena are related to galectins, i.e., development, differentiation, morphogenesis, tumor metastasis, apoptosis, RNA splicing, and immunoregulatory function ( 2 , 3 ).…”