MADRID, 12 Dic. (EUROPA PRESS) –
Compared to chimpanzees, our closest evolutionary cousins, humans are particularly prone to developing advanced carcinomas (the type of tumors that include prostate, breast, lung, and colorectal cancer) even in the absence of known risk factors, such as predisposition. genetics or tobacco use. Now, a study led by researchers at the University of California San Diego School of Medicine and the Moores Cancer Center (United States) has helped explain why.
The study, published in the scientific journal ‘FASEB BioAdvances’, suggests that an evolutionary genetic mutation unique to humans could be, at least in part, to blame. “At some point in human evolution, the Siglec-12 gene (and more specifically, the Siglec-12 protein that it produces as part of the immune system) underwent a mutation that eliminated its ability to distinguish between the ‘me’ and invading microbes , so the body needed to get rid of it. But it has not completely disappeared from the population … it seems that this dysfunctional form of the protein has become a problem and has now become a disadvantage for the minority of people who they still produce it, “argues the study’s lead author Ajit Varki.
In a study of normal and cancerous tissue samples, researchers found that approximately 30 percent of people who still make Siglec-12 protein have more than twice the risk of developing advanced cancer during their lives, compared to people they cannot produce Siglec-12.
Normally, the genes that code for these dysfunctional proteins are eliminated by the body over time, and approximately two-thirds of the global human population has stopped producing the Siglec-12 protein. In cases where the gene is still present in humans, it was long thought to have no functional relevance, and there have been very few follow-up studies during the two decades since it was discovered. Meanwhile, chimpanzees continue to produce working Siglec-12.
When the team set out to detect Siglec-12 in non-cancerous tissue samples using an antibody to the protein, about 30 percent of the samples tested positive, as expected from the genetic information. In contrast, most advanced cancer samples from the same populations tested positive for Siglec-12 protein.
Looking at a different population of patients with advanced-stage colorectal cancer, the researchers found that more than 80 percent had the functional form of the Siglec-12 gene, and those patients fared worse than the minority of patients who did not. “These results suggest that the minority of individuals who can still make the protein have a much higher risk of having advanced cancer,” they detail.
The researchers also validated their findings in mice by introducing tumor cells engineered to produce Siglec-12. The resulting cancers grew much faster and activated many biological pathways known to be involved in advanced cancers, compared to control tumor cells without functioning Siglec-12.
According to scientists, this information is important because it could be used for future diagnoses and treatments. The team made an initial leap by developing a simple urine test that could be used to detect the presence of the dysfunctional protein. “And we might also be able to use antibodies against Siglec-12 to selectively deliver chemotherapies to tumor cells that carry the dysfunctional protein, without harming non-cancer cells,” they conclude.
–
