Mass spectrometry is often used to detect the precise location of cancer after a tumor has formed. Laura Sanchez’s research is heading her in the opposite direction, utilizing the technology’s chemistry before a tumor grows so that drugs can be used to more successfully treat the disease in areas that may have been overlooked.
Sanchez, PhD, a member of the University of Illinois Cancer Center’s Cancer Biology Program and assistant professor of pharmaceutical sciences, has received a $1.9 million five year grant from the National Cancer Institute (ACC 19-214) to conduct her latest research on ovarian cancer. Joanna Burdette, PhD, professor of pharmaceutical sciences and Associate Dean for Research and Graduate Programs in the UIC College of Pharmacy, and a member of the UI Cancer Center’s Cancer Biology program, will serve as co-principal investigator on the grant.
Emerging evidence indicates that high grade serous ovarian cancer (HGSOC) – the most common and deadliest form of ovarian cancer – begins in the epithelium of the fallopian tube. The tumors’ presence in the ovary suggests its primary spread to other organs throughout the body. Preliminary data compiled by Burdette identified that transplanting cells or tissues from one species to another – called xenografting – near the ovary contributes to the aggressiveness of the disease. The tumor cells, she said, spreads to the peritoneal organs, primarily the omentum.
“We believe that the biological problem of primary and secondary high grade serous cancer metastasis is partially caused by chemical communication between the cancer cells and the metastatic organ,” Sanchez said.
Employing mass spectrometry, Sanchez’ laboratory has enhanced 3D cell culture models derived from the fallopian tube and changed them so they can identify the communication that begins from the small molecules known as metabolomics during primary colonization of the ovary that spreads the cancer to the omentum, the sheet of fatty tissue that stretches over the abdomen. Several metabolites that enhanced high grade serous tumor migration, invasion, and adhesion to the ovary were identified through the technology, Sanchez said.
Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system, according to the American Cancer Society. A woman’s risk of getting ovarian cancer during her lifetime is about one in 78. Her lifetime chance of dying from the disease is about one in 108 (the statistics don’t reflect low malignant potential ovarian tumors).
In the UI Cancer Center’s catchment area – Cook County – 11 out of 100,000 women were diagnosed with ovarian cancer from the years 2013-2017, the latest figures available from the Centers for Disease Control and Prevention; 11.8 out of 100,000 were white, compared to 11.1 per 100,000 Black. Ovarian cancer mortality rates in Cook County numbered seven per 100,000 women for the years 2013-2017, with 7.3 per 100,000 being white and 7.1 per 100,000 being Black.
Sanchez’ study will disclose the methods that allow the tumor cells in the fallopian tube epithelium to seize the stress hormone norepinephrine that is produced by the ovary to increase their ability to enter and cling to the reproductive organ during the initial spread of the disease. The research will be conducted using both mouse and human cell models derived from the epithelium, with the tumors being treated with beta adrenergic receptor antagonists to try and translate the findings that will provide a new way to block ovarian colonization, Sanchez said.
By using proteomics in collaboration with co-investigator Stephanie Cologna, PhD, assistant professor of chemistry at the University of Illinois at Chicago, Sanchez will also identify and describe a newly discovered protein that is secreted from tumor cells in the fallopian tube that are responsible for producing ovarian norepinephrine causing the attack and bonding of tumor cells, along with the genetic deletion of the protein from the fallopian tube’s epithelium. This will be used to study the role in ovarian colonization. The team will also build upon their existing technologies of 3D organ and tumor cell communication models and expand into secondary metastasis.
“We have now optimized our technology for co-culture of the omentum together with tumor cell models and have an inventory of metabolites that are unique and do not include norepinephrine,” Sanchez said. “Instead, a novel metabolite found to be produced in significantly more abundance when tumor cells were grown with the omentum corresponded to folate, the ligand for the folic acid receptor that is overexpressed in the tumor cells.
“Taken together, our innovative experimental approach will yield new pathways and targets to mitigate primary metastasis of high grade serous cancer to the ovary.”