Lectins are carbohydrate (sugar)-binding proteins (not to be confused with glycoproteins, which are proteins containing sugar chains or residues). Lectins have been found in plant, viruses, microorganisms and animals. Lectins serve many different biological functions in animals, from the regulation of cell adhesion to glycoprotein synthesis and the control of protein levels in the blood. They have been classified according to their carbohydrate-binding specificity. They may also bind soluble extracellular and intercellular glycoproteins.
Carbohydrates are defined as organic compounds composed of carbon, hydrogen, and oxygen that are organized into ring structures. Lectin-carbohydrate (cellular glycoconjugate) recognition is operative in biochemical information transfer. Changes in glycan structures and the interactions of these structures with endogenous carbohydrate-binding lectins are now considered to be potential biomarkers on cancer cells for monitoring tumor progression.
Tumor cells have abnormal expression of lectins. The level of cell surface lectins increases after normal cells are transformed by oncogenes. Certain carbohydrate-binding lectins, called galectins, are present in tumor cells and even in pre-malignant lesions with a high-risk of progression. Galectins constitute a family of beta-galactoside-binding lectins (galectin1-15) with conserved features in the binding site. The tumor cell surface galectins might be involved in cell-cell adhesion, cell attachment to substratum, anchorage-independent growth, and blood-borne metastasis. Galectins also appear to exhibit various roles in immune responses. Galectin-1 and galectin-3 are the best studied galectins in oncology and galectin-3 is the only member of the galectin family that can form homodimers and homopentamers through intermolecular interactions involving the N-terminal domain. Galectin-3 multimers can cross-link cell surface glycoconjugates (glycoproteins or glycolipids) causing activation of cell signaling pathways.
Galectin-3 is a sticky, cell surface molecule that plays an important role in several rate-limiting steps of cancer metastasis such as metastatic cell adhesion to bone marrow endothelium, homotypic tumor cell aggregation, and clonogenic survival and growth. When present at normal levels, galectin-3 regulates cellular growth and communication. However, elevated galectin-3 levels are directly linked with the development, progression and metastasis of many cancers. Galectin-3 enables cancer cells to adhere to the walls of blood vessels. It also kills activated T-cells, which helps the cancer cells to spread throughout the body and evade the immune system. Galectin-3 also inhibits anticancer drug-induced apoptosis.
Recent studies have shown that elevated serum galectin-3 can be a reliable diagnostic marker in metastatic prostate cancer and thus, one of the target proteins of prostate cancer treatment. Currently incurable, prostate cancer metastasis has a remarkable ability to spread to the skeleton. Patients with metastatic prostate cancer commonly have increased serum galectin-3 concentrations. However, in prostate cancer tissue, galectin-3 expression has been shown to decrease with progression of disease. It is quite the opposite.
Furthermore, AR (androgen receptor)-expressing prostate cancer cells have no endogenous expression of galectin-3; however, AR-non-expressing prostate cancer cells have strong expression of galectin-3. Redistribution/relocalization of galectin-3 was also reported in prostate cancers. These results suggest that galectin-3 exerts opposite biological activities according to its cellular localization and AR expression. It seems that nuclear galectin-3 plays antitumor functions and cytoplasmic galectin-3 promotes tumor progression.
Androgen deprivation therapy (ADT) is generally the initial treatment for men with metastatic prostate cancer. Despite initial response rates of 80 to 90%, nearly all men eventually develop incurable, progressive disease following ADT; this is referred to as androgen-independent (castrate-resistant or hormone-refractory) prostate cancer. It is now clear that progression from localized androgen-dependent prostate cancer to incurable, metastatic androgen-independent (castrate-resistant) prostate cancer is driven by continued androgen-receptor (AR) signaling independently of androgen.
Galectin-3 function is regulated, in part, by proteolytic cleavage of the linker sequence that destroys galectin-3 multivalency while preserving carbohydrate-binding activity of the carbohydrate recognition domain (CRD). Prostate-specific antigen (PSA) was demonstrated to cleave galectin-3 and produce a functionally active, monovalent lectin. Furthermore, the levels of galectin-3 expression in the cancer cells were significantly associated with PSA relapse. PSA may regulate galectin-3 function during prostate cancer progression.
All the above findings indicate that in the case of high ratio of galectin-3 expression in prostate cancer cells, therapies targeting inhibition of both galectin-3 and PSA could be considered to favor the treatments for advanced prostate cancers.The main aim of ProstaZym remedy is to reduce the levels of PSA. ProstaZym can dramatically reduce the PSA levels in patients with either localized prostate cancer or metastatic castrate-resistant (hormone resistant) prostate cancer. Metastatic castrate-resistant prostate cancer is presently a death sentence associated with mean survival rates of 1 year for patients.
It has been demonstrated that inhibition of Galectin-3 functions helps to suppress the progression of prostate cancer. Oral administration of modified citrus pectin, an inhibitor of Galectin-3, significantly reduced lung metastasis of prostate cancer. Modified citrus pectin (MCP) is a form of pectin which is modified enzymatically, reducing its molecular weight to less than15 kDa and esterification to less than 10 percent. These adjustments significantly increase the bioavailability of MCP by allowing it to enter the circulation from the GI tract; they also give MCP greater bioactivity in binding to galectin-3. MCP appears to attach to galectin-3. Pectic polysaccharides from other dietary sources and glycoproteins from polar fish, such as northern cod, are also galectin-3 inhibitors. However, because the role of galectin-3 in the progression of prostate cancer remains largely unknown, some caution is warranted.