Changes in normal cellular metabolism promote metastasis of ovarian cancer cells

A systematic examination of the tumor and the tissues around it — especially normal cells in that tissue, called fibroblasts — reveals a new therapeutic target that has the potential to prevent rapid spread and poor prognosis for high-grade serous carcinoma (HGSC), a type
of tumor that originates primarily in the fallopian tubes or ovaries and spreads throughout the abdominal cavity.

High-grade serous carcinoma is the most common form of ovarian cancer and the
most deadly.

"Until recently, scientists focused on the tumor itself," said Ernst Lengyel, senior author of the study, who is MD, Ph.

In close collaboration with Dr.

Coscia explains: "This is the first time we have been able to distinguish between molecular changes in cancer cells and molecular changes
that occur in adjacent interstitium during disease development.

These metastatic changes were visible in all patients analyzed
.

In the process, they discovered a metabolic enzyme, nicotinamide N-methyltransferase (NNMT), which is highly expressed
in the matrix surrounding metastatic cancer cells.

Researchers are now using high-throughput screening to find new ways
to inhibit this enzyme.

They also found that inhibiting NNMT activity decreases or even reverses the tumor-promoting effects of many cancer-associated fibroblasts
.

Coscia, co-first author of the manuscript and leader in proteomic analysis, added: "This approach could be used to discover other proteins that are important for metastasis and to identify early changes
in the course of disease development.

Mark A.