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Galectin-3 is a member of the lectin family, of which 14 mammalian galectins have been identified.[1] Galectin-3 is approximately 30 kDa and, like all galectins, contains a carbohydrate-recognition-binding domain (CRD) of about 130 amino acids that enable the specific binding of β-galactosides.[1][2][3][4] Galectin-3 is encoded by a single gene, LGALS3, located on chromosome 14, locus q21–q22.[1][5] It is expressed in the nucleus, cytoplasm, mitochondrion, cell surface, and extracellular space.[1][2][3] This protein has been shown to be involved in the following biological processes: cell adhesion, cell activation and chemoattraction, cell growth and differentiation, cell cycle, and apoptosis.[1] Given galectin-3’s broad biological functionality, it has been demonstrated to be involved in cancer, inflammation and fibrosis, heart disease, and stroke.[1][4][6][7] Studies have also shown that the expression of galectin-3 is implicated in a variety of processes associated with heart failure, including myofibroblast proliferation, fibrogenesis, tissue repair, inflammation, and Ventricular remodeling.[6][8][9]

The roles of galectins and galectin-3, in particular, in cancer have been heavily investigated.[10] Of note, galectin-3 has been suggested to play important roles in cancer metastasis.[11]

Role in Disease[edit]


Research has shown a definite correlation between galectin-3 expression levels and various types of fibrosis. Galectin-3 is upregulated in cases of liver fibrosis, renal fibrosis, and idiopathic pulmonary fibrosis (IPF). In several studies with mice deficient in or lacking galectin-3, conditions that caused control mice to develop IPF, renal, or liver fibrosis either induced limited fibrosis or failed to induce fibrosis entirely.[12][13][14] Companies have developed galectin modulators that block the binding of galectins to carbohydrate structures. The galectin-3 inhibitor, TD139 has the potential to treat fibrosis.[14]

Galectin-3 inhibitor[edit]

Galectin-3 is upregulated in patients with idiopathic pulmonary fibrosis. The cells that receive galectin-3 stimulation (fibroblasts, epithelial cells, and myofibroblasts) upregulated the formation of fibrosis and collagen formation.[15] Fibrosis is necessary in many aspects of intrabody regeneration. The myocardial lining constantly undergoes necessary fibrosis, and the inhibition of galectin-3 interferes with myocardial fibrogenesis. A study concluded that drugs binding to galectin-3 will benefit those who have too much fibrosis on the heart, but it might potentially backfire for those who need heart restructuring.[15]

Cardiovascular Disease[edit]

Elevated levels of galectin-3 have been found to be significantly associated with higher risk of death in both acute decompensated heart failure and chronic heart failure populations.[16][17][18][19] In normal human, murine, and rat cells galectin-3 levels are low. However as heart disease progresses, significant upregulation of galectin-3 occurs in the myocardium.[20]

Galectin-3 also may be used as a biomarker to identify at risk individuals, and predict patient response to different drugs and therapies. For instance, galectin-3 levels could be used in early detection of failure-prone hearts and lead to intervention strategies including broad spectrum anti-inflammatory agents.[21] One study concluded that individuals with systolic heart failure of ischaemic origin and elevated galectin-3 levels may benefit from statin treatment.[22] Galectin-3 has also been associated as a factor promoting ventricular remodeling following mitral valve repair, and may identify patients requiring additional therapies to obtain beneficial reverse remodeling. [23]

Galectin-3 and Cancer[edit]

The wide variety of effects of galectin-3 on cancerous cells are due to the unique structure and various interaction properties of the molecule. Overexpression and changes in the localization of galectin-3 molecules affects the prognosis of the patient and targeting the actions of galectin-3 poses a promising therapeutic strategy for the development of effective therapeutic agents for cancer treatment.

Overexpression and changes in sub- and inter-cellular localization of galectin-3 are commonly seen in cancerous conditions. The many interaction and binding properties of galectin-3 influence various cell activities based on its location. Altered galectin-3 expression can affect cancer cell growth and differentiation, chemoattraction, apoptosis, immunosuppression, angiogenesis, adhesion, invasion and metastasis.[24]

Biological effects[edit]

Galectin-3 overexpression promotes neoplastic transformation and the maintenance of transformed phenotypes as well as enhances the tumour cell's adhesion to the extracellular matrix and increase metastatic spreading. Galectin-3 can be either an inhibitory or a promoting apoptotic depending on its sub-cellular localization. In immune regulation, galectin-3 can regulate immune cell activities and helps contribute to the tumour cell's evasion of the immune system. Galectin-3 also helps promote angiogenesis.[24]

Clinical applications[edit]

Galectin-3 is increasingly being used as a diagnostic marker for different cancers. It can be screened for and used as a prognostic factor to predict the progression of the cancer. Galectin-3 has varying effects in different types of cancer.[25] One approach to cancers with high galectin-3 expression is to use small molecule inhibition of galectin-3 to enhance treatment response.[26]

Research on Galectin-3[edit]

Galecto Biotech is a research company focused on developing drugs using galectin-3 in treatment for fibrosis, specifically idiopathic pulmonary fibrosis.[27] Galectin Therapeutics in the United States is also using galectins for their research, finding recently that inhibition of galectin-3 significantly reduces portal hypertension and fibrosis in mice.[28] Chronic heart failure has been found to be indicated by a galectin-3 tests, using the ARCHITECT immunochemistry platform developed by Abbott and BG Medicine, helping to determine which patients are most at risk for the disease.[29] Pecta-Sol C binds to galectin-3 binding sites on the surfaces of cells as a preventative measure created by Isaac Eliaz in conjunction with EcoNugenics.[30]


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