Ovarian cancer often spreads early because it grows in the tissues that cover the ovaries and from there, it can easily spread to the bowels or abdominal lining. It can also affect other areas of the body, including the lungs or liver.
A team of researchers from the University of California and the University of Notre Dame used electron microscopy and live imaging to learn about the cellular mechanisms that trigger ovarian cancer to spread, or rather metastasize. The research was led by M. Sharon Stack, a Kleiderer-Pezold professor of biochemistry and director of Notre Dame Harper Cancer Research Institute, and Mark Alber, a professor of applied mathematics at UC Riverside. In their most recent paper, the researchers discuss how a group of proteins, known as cadherins, make it possible for cancer cells to spread to different areas of the body. Furthermore, they discuss how it may be feasible to obstruct the process of metastasis by obstructing the cadherin activity.
A difference in cells
As ovarian tumors spread, they give off cells known as multicellular aggregates (MCAs) within the abdomen and pelvis. In order to study the complete process of metastasis, researchers looked at the relationship between epithelial ovarian cancer (EOC) cells and 3D models of the abdominal wall. They found the EOC cells take on N-cadherin (Ncad), which is an occurrence that allows EOC cells to penetrate through and attach to the abdominal wall. What’s more, they found that MCAs split up before the invasion of cancer cells, portraying that cell-cell junction integrity is necessary for complete metastasis. Professor Mark Alber notes that ovarian cancer cells do not seem to present a “leader-follower” approach when it comes to a clustered cell invasion. “Interestingly, co-culture of Ncad-expressing cells with cells expressing E-cadherin (Ecad) did not promote invasion of the Ecad-expressing cells, demonstrating that Ncad-expressing cells do not simply lead the way for other cell populations to follow” said Professor Sharon Stack.
The researchers’ findings indicate the significance of Ncad in metastasis of ovarian cancer and support prior clinical studies, which suggest that Ncad-blocking molecules can be used as a form of treatment to slow down or prevent EOC growth altogether. The research team plans to use their findings in order to further learn about metastasis of ovarian cancer and develop computerized models of cancer cell invasions. Additional studies will use samples of patients, provided by research partners from City of Hope in Duarte, along with experimental motions to gain new perspectives into the molecular mechanisms that trigger metastasis of ovarian cancer and to discover new treatment approaches.
Ovarian cancer statistics
The American Cancer Society estimates that this year, over 22,000 women in the United States will receive a diagnosis of ovarian cancer. Ovarian cancer can develop in different areas of the ovary – the stromal, germ, or epithelial cells. The stromal cells are the cells that form the substance of the ovary, the germ cells are the cells that become the eggs, and the epithelial cells are the cells that make up the outer layer of the ovary. Ovarian cancer mainly occurs in older women, aged 63 and above. It is also more common in Caucasian women that it is in African-American women.
Discovering early-stage ovarian cancer
Ovarian cancer of an early stage typically does not present any obvious symptoms. However, it can trigger a few symptoms such as:
- Feeling bloated
- Having difficulty eating
- Experiencing abdominal pain or discomfort
- Experiencing a frequent need to urinate
Epithelial cell carcinoma is the most common form of ovarian cancer and it makes up more than 85% of ovarian cancers. Moreover, it is the 4th most common cause of cancer death in women. This form of ovarian cancer is more common in women who:
- Have a family history of ovarian cancer
- Have a family history of both breast cancer and ovarian cancer
- Have a family history of colorectal cancer and ovarian cancer
- Are predisposed to breast cancer genes – BRCA1 and BRCA2
Ovarian cancer is the 9th most common cancer, with over 20,000 diagnoses made each year. The main reasons why ovarian cancer is difficult to diagnose and treat early on are due to the following.
Rapid spreading of the disease
Ovarian cancer does not present any symptoms in the early stages. For this reason, over 70% of women are diagnosed with the disease at an advanced stage (stage III or stage IV), when the cancer has spread within the abdomen and pelvis. At this point, the cancer can be rather difficult to treat and it is often fatal. “The symptoms of ovarian cancer are not very specific. And that's one of the major challenges that leads to the majority of women being diagnosed at a later stage. Many of the symptoms are vague, such as abdominal discomfort, frequent urination, bloating, that will cause heartburn - these are symptoms that are vague that you really cannot ascribe to ovarian cancer. So if someone has any of these symptoms, the advice is to take them seriously and seek help as soon as possible” said Dr. Kunle Odunsi, Deputy Director of Rosewell Park Cancer Institute. Unfortunately, to date, there are no reliable approaches to early-stage detection of ovarian cancer.
Limited screening and treatment approaches
Nowadays, the most common tools used to screen for ovarian cancer are: pelvic exam, transvaginal ultrasound, CA-125 test and other blood tests. Most healthcare experts agree these current detection tools are not successful enough for accurately identifying and diagnosing ovarian cancer. This is due to the fact that research studies have yet to discover reliable screening methods, unless a woman is at high risk of ovarian cancer due to a family history of the disease with predisposed BRCA1 and BRCA2 genes. Moreover, there are limited treatment approaches to ovarian cancer when it has reached stage III or stage IV. At the point, the cancer may be incurable.
“There are two screening tools for the early detection of ovarian cancer. And unfortunately, both have important limitations. One is a very clinical application, a transvaginal ultrasound, where the doctor just basically visualizes the pelvic area for evidence of disease. Unfortunately, through the visualization, the doctor cannot distinguish between benign ovarian disease or malignant ovarian disease, which is ovarian cancer.The second screening test is a blood test for a marker called CA-125, which is elevated in most - but not all - patients with ovarian cancer. Unfortunately, it is also elevated in women with benign conditions, such as benign cysts, endometriosis, or liver disease, or sometimes elevated in women who are currently menstruating. So it's also a limitation that some women with ovarian cancer do not have elevated levels of this marker” said Dr. Kirsten Moysich, Professor of Oncology at Roswell Park and Co-leader of the Roswell Gynecological Cancer Disease-Site Research Group.
When diagnosed with ovarian cancer, it is important to be proactive. Genetic testing is highly recommended when striving to identify the risks associated with ovarian cancer. “So that will allow the individual to make an informed decision about what to do next, whether to do something to prevent further development of ovarian cancer, such as lifestyle modification, the use of the birth control pill, or to consider risk-reducing surgery. So those are some of the options that are out there. But those decisions are better made in the context of genetic counseling” said Dr. Kunle Odunsi.