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

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.

Source:

• Iwanicki MP, Davidowitz RA, Ng MR, et. al. Ovarian Cancer Spheroids Use Myosin-Generated Force to Clear the Mesothelium. Cancer Discovery June 14, 2011 ; published online first June 14, 2011; doi:10.1158/2159-8274. CD-11-0010.

• Scientists Image Beginning Stages of Ovarian Cancer Growth with Time Lapse Technique, Press Release, American Association For Cancer Research, June 14, 2011.

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.