Tag Archives: ovarian cancer metastases

Harvard Scientists Image Beginning Stages of Ovarian Cancer Metastasis; Cancer Cells Bully Their Way Through Normal Tissue

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According to a study reported in the Cancer Discovery journal, scientists at Harvard University imaged the beginning stages of ovarian cancer metastasis, and identified a mechanism used by cancer cells to bully their way through normal tissue.

Scientists at Harvard University have created a laboratory model using time-lapse video microscopic technology that allows observation of early stages of ovarian cancer metastasis.

Joan Brugge, Ph.D., Professor & Chair, Cell Biology Department, Harvard University.

“We were able to observe key molecular mechanisms that are necessary for the force-dependent processes associated with metastasis,” said Joan Brugge, Ph.D., professor and chair of the Cell Biology department at Harvard University.

These findings are published in Cancer Discovery, the newest journal of the American Association for Cancer Research (AACR). According to Brugge, who served as program chairperson for the AACR 102nd Annual Meeting 2011, ovarian cancer cells spread throughout the peritoneum by attaching to the outer cell layer of organs in this area and then clearing away this layer of cells and embedding themselves on the organ, where they then proliferate and expand.

“The reason these tumors are so morbid is that the metastatic tumors grow large enough to interfere with the function of the organs in the peritoneum,” she said.

By using the time-lapse video microscopic technique, Brugge and colleagues were able to visualize the detailed sequence of events associated with insertion of tumor cells into peritoneal monolayers in cell culture, and then determine that the mechanism involves tumor cells’ use of force via αlpha-5  beta-1 integrin, talin I and muscle myosin II. These results suggest that ovarian tumor cell clusters gain access to the submesothelial environment by exerting force on the mesothelial cells lining target organs, driving migration and clearance of the mesothelial cells.

Researchers also determined that blockade of force-conducting molecules, including alpha-5 beta-1 integrin, talin I, and nonmuscle myosin II, in the ovarian cancer cells abrogated mesothelial displacement from underneath attached cancer cells.

“Theoretically, by targeting these molecules, it may be possible to prevent the formation of new metastatic tumors,” said Brugge.

The study was funded by The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the National Institutes of Health.

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About the American Association for Cancer Research (AACR)

The mission of the AACR is to prevent and cure cancer. Founded in 1907, the AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries. The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. Including Cancer Discovery, the AACR publishes seven major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. AACR journals represented 20 percent of the market share of total citations in 2009. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists.

Increased Ovarian Cancer Metastases Identified In Women With BRCA Gene Mutations; May Shed Light on New Treatment Approach

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U.K. researchers have found that patients with hereditary ovarian cancer – whose tumors are caused by faulty BRCA1 or BRCA2 genes – are more likely to experience metastases of the liver, lung, spleen, and viscera. … [T]he researchers suggest that ovarian cancer patients whose tumors spread to the solid organs … should be tested for the faulty genes – BRCA1 and BRCA2 – to ensure they are given the most appropriate treatment.

Dr. Charlie Gourley, Acting Head, Medical Oncology, University of Edinburgh Cancer Research Centre

U.K. researchers have found that patients with hereditary ovarian cancer – whose tumors are caused by faulty BRCA1 or BRCA2 genes – are more likely to experience metastases of the liver, lungs, spleen, and viscera. This is despite the fact that their overall prognosis is better than other ovarian cancer patients.  The research is published in the April 20th online edition of the Journal of Clinical Oncology.

In the study, researchers discovered that the percentage of women with BRCA1 or BRCA2 gene mutations who experienced visceral, liver, lung, and splenic metastases were 58%, 42%, 16%, and 32% , respectively, as compared with 5%, 0%, 0%, and 3%, respectively, in non-BRCA gene deficient women.  The researchers note that sporadic (i.e., non-hereditary) ovarian tumors tend to remain within the lining of the abdomen and pelvis.

Based upon the study findings, the researchers suggest that ovarian cancer patients whose tumors spread to the solid organs such as the liver, lungs, and spleen should be tested for the faulty genes – BRCA1 and BRCA2 – to ensure they are given the most appropriate treatment.  For example, patients with hereditary tumors, which account for 10 per cent of ovarian cancers, may be suitable for trials of a new drug called olaparib [AZD2281], which has fewer side-effects than normal cancer treatments. Olaparib belongs to a class of drugs known as “PARP” (Poly (ADP-ribose) polymerase) inhibitors.

Researchers say the study findings will improve the detection of faulty BRCA genes, as current criteria for genetic testing may miss as many as two-thirds of ovarian cancer patients carrying the mutated genes.  Improving the identification of BRCA mutations will help relatives of ovarian cancer patients, who may themselves be at increased risk of developing hereditary ovarian cancer.

Dr. Charlie Gourley, who led the research at the University of Edinburgh, said:

“We are beginning to understand the importance of tailoring cancer treatments according to the specifics of each patient’s tumor. These findings demonstrate that tumors which arise because of defects in the BRCA1 or BRCA2 genes behave differently to other ovarian cancers. This information should also help us to identify the patients carrying these genetic mutations, give them the most effective treatment for their cancer and offer their relatives genetic counselling.”

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