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Lymphatic vessels surrounding tumors play a key role in cancer spread

BOSTON, April 25, 2002 - Scientists at Massachusetts General Hospital (MGH) have discovered that metastasis, or spreading, of cancer cells depends upon lymphatic vessels at the margins of tumors, not those within the tumor itself, as had been speculated. The results, which will appear in Science magazine, was published April 25 on the Science Express website.

"These findings suggest new strategies for cancer treatment," says Rakesh Jain, PhD, of the MGH Department of Radiation Oncology. "Lymphatics at the tumor periphery are sufficient to carry cancer cells to other parts of the body, so these structures should be the targets of therapy."

The lymphatic system plays an important role in immune function, with its network of vessels and nodes that transport a fluid called lymph throughout the body. Like blood vessels, though, lymphatic vessels may act as a conduit through which cancer cells spread. If cancer cells metastasize from a tumor mass to a lymph node, the patient's prognosis is often poor.

Previous studies of lymphatic vessels within tumors have provided mixed results. Although lymphatic structures have been identified, lymphatic vessels within tumors have not appeared to be functional. Jain and his colleagues have now shown that only collapsed lymphatic structures reside within a tumor mass and there are no functional vessels. The collapsed structures may contribute to the high pressure found within tumors, which can impair blood flow and keep drugs from entering the tumors.

The MGH scientists have been conducting studies with a protein called vascular endothelial growth factor-C, or VEGF-C, which stimulates the formation of lymphatic vessels and also promotes blood vessel formation in some tumors. "By neutralizing VEGF-C at the tumor margins, we can potentially have a double effect," says Jain. Hindering both blood vessel and lymphatic vessel formation may effectively block tumor metastasis. While Jain's research was initiated in animals, the findings were confirmed in lung tumors from human patients.

The other members of the MGH research team are first author Timothy Padera, BS, Ananth Kadambi, PhD, Emmanuelle di Tomaso, PhD, Carla Mouta Carreira, PhD, Edward Brown, PhD, Yves Boucher, PhD, Noah Choi, MD, Douglas Mathisen, MD, John Wain, MD, Eugene Mark, MD, and Lance Munn, PhD. The study was supported by research grants from the National Institutes of Health.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $300 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine. In 1994, the MGH joined with Brigham and Women's Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.

Media Contact: Susan McGreevey , MGH Public Affairs
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