Virtually all human cancers experience a state called intra-tumoural hypoxia, or a low amount of oxygen within the tumour. In the study, researchers showed that the HPV-positive cancers adapted to and took advantage of the hypoxic environment by expressing a protein that activates a cell signalling pathway that helps the cancers survive, grow and spread.
The research, done on cells in culture and in animal models, may lead to the development of new therapies that target the cell signalling pathway, thereby interrupting ability of the cancer cells to thrive, said Matthew Rettig, senior author of the study.
In those cases where a cancer is HPV-positive the virus will make the disease more aggressive and deadly. “The virus appears to be regulating the expression of genes that control all of the characteristics of hypoxic tumours, those that promote survival, drug resistance and the spread of the cancers,” Rettig added. “It is good for the tumour, bad for the patient.”
In HPV-associated cancers, the HPV DNA is integrated into the cancer cell’s genome, where it expresses a protein called E6. In the cancer cell’s hypoxic environment, the protein targets a cell signalling pathway, heightening its activation, Rettig said. This is the first time an association has been shown between the virus and hypoxia-induced activation of the cell signalling pathway.
The findings in the study happened by coincidence, Rettig said. He and his team were screening different cancer cell types for hypoxia-induced activation of the cell signalling pathway. When he looked at the results, Rettig noted that only the cancer cell types that were were HPV-positive had heightened activation of the pathway. Cervical and head and neck cancers not caused by HPV did not have heightened activation of the pathway. “The cells had to have the virus to have the activation,” he said.
MEDICA.de; Source: University of California, Los Angeles (UCLA), Health Sciences