Galectins are a class of proteins made by many cells in the body, but predominantly in cells of the immune system. As a group, these proteins are able to bind to sugar molecules that are part of other proteins — glycoproteins — in and on the cells of our body. Galectin proteins act as a kind of molecular glue, bringing together molecules that have sugars on them. There are 15 galectin protein subtypes, all with the common characteristic of binding to galactose-containing carbohydrates and glycoproteins.
Galectin-3 has many effects, such as modulating the interaction of cells and receptors, the immune response, the behavior of cancer cells, inflammation, and scarring of organs.
Galectin proteins, in particular galectin-3, are known to be markedly increased in a number of important diseases including inflammatory diseases, scarring of organs (e.g. liver, lung, kidney, and heart) and cancers of many kinds. The increase in galectin protein promotes the disease and is detrimental to the patient.
Published data substantiating the importance of galectin-3 in the fibrotic process arises from gene knockout experiments in animal studies. Mice genetically altered to eliminate the galectin-3 gene, and thus unable to produce galectin-3, are incapable of developing liver fibrosis in response to toxic insult to the liver and in fatty liver disease as well as development of fibrosis in other tissues.
Medical science is recognizing the role that galectin-3 plays in a wide range of diseases. There were 7 scientific articles written about galectin-3 in 1990, 61 in 2000, 148 in 2010, and 334 in 2018. These articles encompass the role of galectin-3 in heart attacks, lung fibrosis, liver fibrosis and cirrhosis, diabetes, cancer, and many other diseases.
Galectin Therapeutics has a lead drug compound that inhibits binding of galectin-3 in an attempt to treat diseases (in particular NASH cirrhosis and cancer) that are dependent on the action of galectin-3.
Galectin proteins, particularly galectin-1 and galectin-3, are present in increased amounts in cancers of many types. In fact, expression of galectin-3 appears to be higher in the vast majority of solid tumors including skin, lung, breast, pancreas, ovarian, colon, thyroid and head and neck, among others.
Examining tumors for galectin-3 has gained some acceptance in clinical medicine. In thyroid cancers, pathologists routinely stain tumor biopsies for galectin-3 to distinguish malignant from normal tissue, potentially reducing unnecessary thyroid surgeries. It has also been shown that the amount of galectin-3 expressed in some cancers correlates with the aggressiveness of the cancer and the ultimate prognosis of the patient, a finding that may be useful in clinical practice.
Galectin-3 promotes the spread of cancer in three ways:
Invasiveness. Galectin proteins help cancer cells move, and therefore they promote the infiltration of the cancer cells into surrounding tissue.
Metastasis. In colon cancer, the highest levels of galectin-3 are found in tumors that have metastasized to elsewhere in the body, and the lowest are in the cancer that’s in the original polyp in the colon.
Tumor growth. Galectin-3 reduces cell death and promotes the growth of blood vessels that bring blood supply to the tumor.
Galectin-3 also inhibits the patient’s immune system, thereby preventing immune cells from killing tumor cells. This immune effect of galectin-3 in cancer is particularly interesting because of the rising importance of cancer immunotherapy.