In a recent study, a team of researchers from the Institute for Research in Biomedicine sought to investigate the molecular makeup of tumors to better understand the disease. Understanding the composition of the tumor at a molecular level would help them formulate better treatments with lesser side effects.
The differences between the survival of cancer cells and their incidences on men and women were investigated. Detailed findings from the study are published in the peer-reviewed journal Science Advances.
The researchers compared the cell composition of brain tumors from flies of both genders at a molecular level and identified certain proteins that were directly responsible for the different levels of aggression exhibited by the cancer.
The main driving factor behind the research was that the incidence of cancer on men and women is not statistically balanced. Until the research little was known as to why this happens. The Institute for Research in Biomedicine (IRB Barcelona) used the vinegar fly, Drosophila melanogaster for the research. The team successfully identified protein regulators at the molecular level that lead to key differences in tumors among males and females.
“We have identified possible regulators responsible for tumor differences between male and female flies,” says Catalan Institution for Research and Advanced Studies (ICREA) researcher Cayetano González. “The results also show that these genes could be potential targets to neutralize their degree of malignancy,” adds the researcher. Mr. Cayetano is also heading the Laboratory of Cell Division at IRB Barcelona.
Significant differences have been found in the incidence and distribution of cancer between men and women during epidemiological studies. The survival of cancer was another factor that was found to vary between the two sexes even when non-reproductive organs were compared.
The research team mapped the cells and drew up physical comparisons of the developmental stages of the tumors in the vinegar flies. Tumors were induced in the brain of the flies and the concentration of specific proteins was taken into account and analyzed over the period of the tumor growth.
A brain tumor in males was found to be more aggressive as compared to the one induced in female flies. The higher expression of the tumor was linked with a set of proteins which were more abundantly found in the male cells as compared to the female ones.
“Many of the possible regulators of sex-dependent differences in tumors that we have identified in our Drosophila model are highly conserved proteins that are also found in humans,” says González.
The protein Phf7, also found in humans, was one of the most pinpointed proteins in the research. The protein was found to be present in the male tumor cells which exhibited higher aggression. Phf7 was absent from the tumor cell samples obtained from the females.
The effect of the protein was confirmed by removing the protein from male flies which led to a remarkable decrease in the aggressiveness of the tumors. The aggressiveness was found to be on par with those of the female tumor cells after the removal of the Phf7.
The study was authored by a postdoctoral researcher at IRB Barcelona Ms. Cristina Molnar. She said, “Our results show that the proteins responsible for the differences in tumors between males and females can be regulated to reduce the degree of malignancy that is associated with the sex of the individual affected,”.
On the selection of Drosophila melanogaster as the test subject, the team said that the fly has been used for cancer studies for decades and the results have been promising. Many cancer treatments have been formulated using experimental models involving the vinegar fly.
“Understanding the molecular basis responsible for the sex-related differences in the incidence and development of cancer may allow us to find specific treatments for men and women,” González adds.
The study has allowed the discovery of many of the proteins that are of great relevance to human cancer. Previously the same techniques were employed by researchers to prepare models for leukemia, neuroblastoma, glioblastoma, ovarian cancer, and many others. The team hopes that the specific treatments that can be prepared based on the findings will help save thousands if not millions of lives.