Ovarian cancer affects approximately 239,000 women annually, worldwide, and results in 152,000 deaths, predominantly in North America and Europe. It is the seventh most common cancer and eighth most common cause of death from cancer in women. A significant reason that ovarian cancer is so deadly is that it reaches an advanced stage before it is detected, having metastasized within the abdomen.

In order to develop better strategies and treatments for ovarian cancer,  scientists are trying to understand the process of metastasis. Interestingly, the metastasis of ovarian cancer differs from other types of tumors because these cancerous cells mainly move within the peritoneal cavity on a superficial level, according to a paper published in The American Journal of Pathology.

These researchers found two types of ovarian carcinoma with differing metastatic profiles. The first (Type I) is a slow growing borderline tumor while the other (Type II) is a more damaging high-grade serous carcinoma that metastasizes quickly. Type II is also genetically unstable and late metastasis of ovarian cancer is depicted by oncogene-driven fast growth of tumor nodules.

Ovarian cancer usually spreads by moving to nearby organs within the peritoneum. The steps of metastasis are complicated but there are some basic phases that cancers appear to follow. All cancers, by definition, invade the tissue of origin, and multiply without constraints, however, in order to metastasize, some cells within the tumor must first stop growing while others continue to divide. Then the non-dividing, cancerous cells break off from the main, localized tumor, invade the bloodstream or lymphatic system and travel to a distant site that provides them with a suitable environment.

What prompts and causes the beginning stages of metastasis is usually found within the signaling pathways of the ovarian cancerous cells. The ScienceDaily publication reports on a study that discovered a scaffolding protein within the signaling pathways causes the growth and metastasis of epithelial ovarian cancer.

The study conducted at the Fox Chase Cancer Center analyzed ovarian cancer in animal models but applied its findings to human cancers as well. The protein NEDD9, which plays a critical role in converting cell adhesion events into intracellular signals was discovered to regulate oncogenic signaling pathways in the cell which stimulate the division and spread of the epithelial ovarian tumors.

“NEDD9 expression is usually associated with metastasis,” lead author Rashid Gabbasov, of Fox Chase’s Developmental Therapeutics Research Program, told the news source.

The researchers used two groups of mice bred to develop ovarian cancer when studying the protein’s role in metastasis. The NEDD9 protein was removed in one group of mice while the other group expressed the compound. With the help of MRI scans, the researchers were able to discover delayed tumor development in the mice that lacked the NEDD9 protein when compared to the control group. Levels of NEDD9 in biopsies of ovarian cancer have recently been correlated with an increased risk of metastasis and consequently poor outcome (Wang el al, Hum Pathol, 45:401-8 (2014)).

Since NEDD9 does not have catalytic activity capable of inhibition, it is not likely to be useful for targeted therapy, and since is also not present in the blood, which makes it counterproductive for diagnosing ovarian cancer.  However, it’s presence in biopsy specimens is a indication that aggressive intervention is warranted. NEDD9 also stimulates other signaling proteins that play a role in cancer development, this discovery is advantageous for future research into metastatic ovarian cancer, and the targeting of related tyrosine kinase based signaling proteins.

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Categories: Oncology

Tags: animal models, NEDD9, ovarian cancer