Galectins are a family of carbohydrate-binding proteins with an affinity for beta-galactosides. Galectin-1 (Gal-1) is differentially expressed by various normal and pathological tissues and appears to be functionally polyvalent, with a wide range of biological activity. The intracellular and extracellular activity of Gal-1 has been described. Evidence points to Gal-1 and its ligands as one of the master regulators of such immune responses as T-cell homeostasis and survival, T-cell immune disorders, inflammation and allergies as well as host-pathogen interactions. Gal-1 expression or overexpression in tumors and/or the tissue surrounding them must be considered as a sign of the malignant tumor progression that is often related to the long-range dissemination of tumoral cells (metastasis), to their dissemination into the surrounding normal tissue, and to tumor immune-escape. Gal-1 in its oxidized form plays a number of important roles in the regeneration of the central nervous system after injury. The targeted overexpression (or delivery) of Gal-1 should be considered as a method of choice for the treatment of some kinds of inflammation-related diseases, neurodegenerative pathologies and muscular dystrophies. In contrast, the targeted inhibition of Gal-1 expression is what should be developed for therapeutic applications against cancer progression. Gal-1 is thus a promising molecular target for the development of new and original therapeutic tools.

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Galectin-1: A Small Protein with Major Functions

REVIEW Galectin-1: a small protein with major functions

Galectin expression in cancer diagnosis and prognosis: a systematic review

Unraveling galectin-1 as a novel therapeutic target for cancer.

Purpose: This study is aimed at investigating the role and novel molecular mechanisms of galectin-1 in lung cancer progression. Experimental Design: The role of galectin-1 in lung cancer progression was evaluated both in vitro and in vivo by short hairpin RNA (shRNA)-mediated knockdown of galectin-1 in lung adenocarcinoma cell lines. To explore novel molecular mechanisms underlying galectin-1–mediated tumor progression, we analyzed gene expression profiles and signaling pathways using reverse transcription PCR and Western blotting. A tissue microarray containing samples from patients with lung cancer was used to examine the expression of galectin-1 in lung cancer. Results: We found overexpression of galectin-1 in non–small cell lung cancer (NSCLC) cell lines. Suppression of endogenous galectin-1 in lung adenocarcinoma resulted in reduction of the cell migration, invasion, and anchorage-independent growth in vitro and tumor growth in mice. In particular, COX-2 was downregulated in galectin-1–knockdown cells. The decreased tumor invasion and anchorage-independent growth abilities were rescued after reexpression of COX-2 in galectin-1–knockdown cells. Furthermore, we found that TGF-β1 promoted COX-2 expression through galectin-1 interaction with Ras and subsequent activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal–regulated kinase (ERK), and NF-κB pathway. Galectin-1 knockdown sensitized lung cancer cells to platinum-based chemotherapy (cisplatin). In addition, galectin-1 and COX-2 expression was correlated with the progression of lung adenocarcinoma, and high clinical relevance of both proteins was evidenced ( n = 47). Conclusions: p38 MAPK, ERK, and COX-2 activation are novel mediators for the galectin-1–promoted tumor progression and chemoresistance in lung cancer. Galectin-1 may be an innovative target for combined modality therapy for lung cancer. Clin Cancer Res; 18(15); 4037–47. ©2012 AACR .

https://clincancerres.aacrjournals.org/content/clincanres/18/15/4037.full.pdf

Galectin-1 promotes lung cancer progression and chemoresistance by upregulating p38 MAPK, ERK and cyclooxygenase-2

Objective: To determine the expression of endogenous adhesion/growth-regulatory lectins and their binding sites using labeled tissue lectins as well as the binding profile of hyalur

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Prognostic Significance of Endogenous Adhesion/Growth-Regulatory Lectins in Lung Cancer

Objective: Measurement of microvascularization and determination of its prognostic significance in cases of lung cancer. Methods: Section prepared from histological material from 432 radically operated non-small cell lung cancer patients were stained with antibodies against factor VIII-associated antigen. During computer imaging, the absolute and relative parameters of the vascularization were determined, as was the density of tumour cells situated in the vicinity of the vessels. The results were compared with the TNM status, the cell type and the survival. Results: Each parameter demonstrated an enhanced vascularization in classifications T2 and T4, but only the surface fraction, the mean vascular circumference and the mean vascular area displayed a significant change. The microvascularization parameters did not differ significantly between with different N status, however, the cell density progressively increased in the areas close to the vessels in advanced pN classifications. Elevation of the tumour cell density within 20 mm distance of the vessels was accompanied by a significantly poorer survival rate. The density of tumour cells within 20 mm region was the second strongest prognostic factor after the N status. Conclusions: More advanced tumour classifications grow with enhanced vascularization. A clear-cut connection cannot be demonstrated between the vascularization and appearance of lymph node metastases. The density of tumour cells measured in the direct vicinity of vessels is an important prognostic factor. Q 2005 Elsevier B.V. All rights reserved.

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Jan Dirk Baumhäkel

Papers

Prognostic Significance of Endogenous Adhesion/Growth-Regulatory Lectins in Lung Cancer

Prognostic significance of microvascularization in cases of operated lung cancer.