Metastasis in Ovarian Cancer Traced to Newly Discovered Signaling Pathway

Metastasis in Ovarian Cancer Traced to Newly Discovered Signaling Pathway

Researchers at Cold Spring Harbor Laboratory (CSHL) published findings that highlight the discovery of a new cancer signaling pathway that may prove useful in the efforts to prevent metastasis in ovarian cancer (OC).

The study, “HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer,” was published in the latest edition of the journal Genes and Development.

About this study

In an effort to better understanding the pathophysiology involved in OC metastasis, the researchers utilized OC cell lines, which are developed from a single cell so they have the same genetic make-up and grown in artificial environments, such as the laboratory.

Using the cell lines, they discovered that a specific protein — known as non-receptor tyrosine kinase feline sarcoma-related (FER) — played an important role in metastasis.  FER was shown to be elevated in OC cells in comparison to cells that were not oncogenic. Also, when researchers suppressed the levels of FER in the OC cell lines, they found that the invasiveness and mobility of these cells slowed, and in some cases were minimized.

These results led researchers to conclude that this was a newly discovered pathway upon which OC metastasis takes place, and that it may indeed be a therapeutic target, possibly in combination with other chemotherapy agents, to prevent advance disease and tumor metastasis.

“The statistics point to the urgent need to address advanced disease — metastasis — in ovarian cancer the problem is especially difficult because of a feature specific to this form of cancer: ovarian cells move around readily within the peritoneal cavity, via the peritoneal fluid, both under normal conditions, and also, unfortunately, when cancer is present,” Dr. Gaofeng Fan, PhD, the study’s first author, said of the discovery’s importance in a CSHL press release. “Thus, in addition to being able to colonize other sites in the body via blood vessels, ovarian cancer cells have another way of migrating. It’s very hard to render patients free of the disease via surgery due to this diffusion feature.”

“We showed FER was essential for ovarian cancer cell motility and invasiveness, both in vitro and in vivo,” said Nicholas Tonks, a CSHL professor and the study’s lead investigator. “[O]ur findings pinpoint an important new signaling hub … This may provide a novel strategy for therapeutic intervention.”

Metastasis in Ovarian Cancer

Advanced OC is a metastasized cancer, meaning that it has spread from the original tumor site, such as the surfaces of the ovary, the fallopian tube, or the membrane lining of the organs cavity. Metastasis is common in ovarian cancer because it often goes undetected. Fully two-thirds of women diagnosed are found to have advanced cancers, Stage 3 or later, the study noted.

Due to its location of tumor origin being in the pelvic cavity, OC often spreads aggressively to other organs within the pelvis and abdomen.