Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities

Abstract

Advanced prostate and bladder cancer are two outstanding unmet medical needs for urological oncologists. The high prevalence of these tumours, lack of effective biomarkers, and limited effective treatment options highlight the importance of basic research in these diseases. Galectins are a family of β-galactoside-binding proteins that are frequently altered (upregulated or downregulated) in a wide range of tumours and have roles in different stages of tumour development and progression, including immune evasion. In particular, altered expression levels of different members of the galectin family have been reported in prostate and bladder cancers, which, together with the aberrant glycosylation patterns found in tumour cells and the constituent cell types of the tumour microenvironment, can result in malignant transformation and tumour progression. Understanding the roles of galectin family proteins in the development and progression of prostate and bladder cancer could yield key insights to inform the clinical management of these diseases.

Comparative Immunohistochemical Study of Galectins 1, 3 and 9 in Ovarian Epithelial Neoplasms

“…When we evaluated Gal-"1" expression in non-benign neoplasms, we found significant expression in peritumoral stroma. Gal-"1" expression is common to several types of cancer, including metastatic tumors [5,12]. We infer that increased stromal expression of Gal-"1" in non-benign tumors relates to behavior of the neoplasia and to the ability of these tumors to invade stroma and generate metastasis.…”

“…It is speculated that Gal-"3" expression plays some role in late-stage tumor progression, favouring chemoresistance and development of metastases [11]. Similarly, increased Gal-"1" expression is common in different types of cancer, particularly in metastatic tumors [5,12]. Gal-"9" is reported to be involved in carcinogenesis in other different tumor [13].…”

How else can we approach prostate cancer biomarker discovery?

“…Spatial analyses at a genetic level demonstrate that PCa progression involves molecular gradients that integrate a stromal response with inflammation [13], and PCa tumors with increased stromal density may be more immunosuppressive [14]. The interaction of the immune system with tumor and stroma is largely influenced by carbohydrate-binding lectins on immune cells and other carbohydrate-binding proteins like galectins [15]. More studies are needed to understand how ECM stromal protein and carbohydrate composition influences the tumorimmune microenvironment.…”

“…The role of the prostate stroma in preventing or promoting effective immune responses to tumor is an active area of research, and it is certainly a contributor to the largely poor responses of prostate cancers to emerging immunotherapy strategies [13,15]. The imaging mass spectrometry approaches developed [11,12] yield unique spatially localized targets integrally linked with molecular changes in the prostate tumor microenvironment.…”

PET/CT Imaging with an 18F-Labeled Galactodendritic Unit in a Galectin-1–Overexpressing Orthotopic Bladder Cancer Model

“…t (triplet), q (quartet), m (multiplet) and br (broadened) 13. C NMR are reported in parts per million relative to the solvent.…”