New research from Texas-based Rice University suggests that tumor cells of the pancreas and uterus are protected by a ‘vicious cycle’ of mucus production that prevents cancer cells from host immune defenses while also stimulating proliferation. The research team observed that the cancer cell protein receptors initiate the mucus production by stimulating production of mucin (a glycoprotein that is also referred to as MUC1). The results of this research are published online in the peer reviewed Journal of Cellular Biochemistry.
Generally, the mucin lines the internal epithelial lining of viscera to prevent infection and damage to the gut, lungs and other organs by obnoxious stimuli (for example protection of stomach lining from the gastric acid). However, when mucin is produced by cancer cells, the mucin lining protects cancer cells by evading host immune responses and chemotherapy targets.
Details of the study:
The research team from Rice’s Wiess School of Natural Sciences is comprised of renowned biochemist and Dean of institute, Dr. Daniel Carson, post doctoral researcher Neeraja Dharmaraj (who is also the lead author of the study) and Brian Engel, who is a graduate student.
The research team identified and concluded that the over-expression of MUC 1 is responsible for a number of tumor-associated activities, such as the progression of tumors, metastatic potential, evasion from host immune defenses, and formation of a feedback loop that is responsible for interaction of MUC1 with epidermal growth factor receptor (EGFR). Cancer cells are capable of utilizing EGFR for spread of cancer cells and immune functions since cancer cells are “subvert systems and find ways to get out of control. They auto-activate EGFR by making their own growth factor ligands, for example, or mutating the receptor so it doesn’t require the ligand anymore. It’s always on.”
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According to Carson, EGFR performs a variety of functions in the tumor cells that result in stimulation of growth, differentiation, and proliferation. He explained that mucin and EGFR promotes the reaction in each other and initiates the vicious cycle.
While discussing the functions and properties of mucin, Carson suggested that mucin is comparable to Teflon in many respects. He added:
“Things don’t stick to it easily, which is normally what you want. It’s a primary barrier that keeps nasty stuff like pathogenic bacteria and viruses from getting into your cells.”
The same property of mucin helps in distant metastasis of cancer cells by enclosing and fully covering the tumor cell, detachment from the primary tumor, and the spreading to other organs. Since mucin fully envelopes the tumor cell, immune cells cannot detect or kill the altered cell.
Rice’s Wiess School of Natural Sciences research team offered a possible solution to this issue:
The research team studied the properties and activities of popular hypoglycemic medication rosiglitazone (categorized under the hypoglycemic class-thiazolidinedione), which is associated with increasing the risk of cardiovascular issues. However, the research conducted by Rice’s Wiess School of Natural Sciences suggested that the drug molecules can actively reduce the expression and activation of MUC1 and also interfere with the EGFR activation.
Carson, a professor of biochemistry and cell biology at Department of Molecular Biology and Biochemistry at the University of Texas MD Anderson Cancer Center, added:
“Chronic use of rosiglitazone can produce heart problems in a subset of patients, but if you’re dying of pancreatic cancer, you’re not worried about the long term. If you can reduce mucin levels in just a few days by using these drugs, they might make cancer cells easier to kill by established methods.”
However, the findings are not absolute, and the assumptions made require aggressive testing and experimentation to ascertain qualitative benefits. Carson said: “We think it’s best to understand all the effects. That might give us a rational way to modify these compounds, to avoid unwanted side effects and focus on what we want them to do.”