A new study has found that blocking vascular endothelial growth factor receptor 3 (VEGFR-3) prevented lymphangiogenesis in a mouse model but had no effect on blood angiogenesis or the survival or function of existing lymphatic vessels. Specifically targeting VEGFR-3 may inhibit tumor metastasis by preventing lymphatic vessel growth by the tumor, the study concludes.
VEGFR-3 plays an important role in embryonic and tumor lymphatic vessel growth. Neutralization of the growth factors that activate VEGFR-3 was known to inhibit lymphangiogenesis in tumors and to reduce metastasis to lymph nodes. These observations suggested that antagonists of VEGFR-3 activation could inhibit lymphangiogenesis thus preventing or reducing tumor metastasis. It was not known whether new lymphatic growth could be specifically blocked without also affecting blood angiogenesis or existing lymphatic vessels.
Melody A. Swartz, Ph.D., of Northwestern University in Chicago (currently of the Swiss Federal Institute of Technology Lausanne), and colleagues demonstrate in a mouse model of skin regeneration that blocking VEGFR-3 activation with a novel antibody, mF4-31C1, can completely and specifically prevent lymphangiogenesis while leaving blood angiogenesis and existing lymphatic vessels unaffected.
"These findings raise the possibility that human VEGFR-3 may be targeted therapeutically … to prevent the undesirable growth of lymphatic vessels, such as tumor-induced lymphatic hyperplasia or lymphangiogenesis," the authors write.
In an editorial, Yoshiyawu Aoki and Giovanna Tosato, M.D., of the National Cancer Institute, discuss the known signaling pathways by which VEFGR-3 is activated and its biologic function in normal and disease processes and note the importance of the new findings.
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Study Finds Evidence That Progesterone Signaling Influences Ovarian Cancer Risk
Variations in the progesterone receptor (PGR) gene, which is involved in progesterone signaling, are associated with an increased risk of ovarian cancer, according to a new study.
The PROGINS allele of the PGR gene has been associated with an increased risk of ovarian cancer and a decreased risk of breast cancer. To refine the association between common variations in the PGR gene and the risk of these two diseases, Celeste Leigh Pearce, of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, and colleagues looked at single nucleotide polymorphisms that capture variation across the gene in women from two ovarian cancer case–control studies and from breast cancer patients and control subjects from a cohort study.
Variation in the PGR gene was associated with the risk of ovarian cancer, but the strongest association was not with the PROGINS allele. Variation in two common haplotypes (4-D and 4-E) was associated with a more than threefold increased risk of ovarian cancer. In addition, there was some evidence that women who carried two copies of the PROGINS allele had a decreased risk of breast cancer. The authors write that these findings may provide evidence that changes in progesterone signaling can influence ovarian cancer risk, which could provide further insight into how the disease could be prevented in the future.
Contact: John Weiner, USC Health Sciences Public Relations, 323-442-2823, jonweine@usc.edu
Dietary Zinc Affects COX-2 Expression and Esophageal and Tongue Carcinogenesis in Rats
A new study finds that rats that are deficient in dietary zinc experience increased expression of COX-2 in the esophagus and tongue, an effect that is accompanied by a hyperplastic phenotype in these areas that is likely relevant to cancer development.
Esophageal and tongue cancers have been associated with dietary zinc deficiency, and these cancers often overexpress COX-2, a characteristic known to contribute to carcinogenesis. Louise Y. Y. Fong, of the Kimmel Cancer Center of Thomas Jefferson University in Philadelphia, and colleagues demonstrate that COX-2 overexpression accompanies hyperplasia in zinc-deficient rats. Treating the rats with zinc or a COX-2 inhibitor reduced COX-2 overexpression and reversed the hyperplasia found in the esophagus. The authors suggest that zinc treatment may have possibility for the prevention of esophageal and oral cancers in people at high risk.
Contact: Steven Benowitz, Thomas Jefferson University, 215-955-5291, steven.benowitz@jefferson.edu
Bone Marker Levels Predictive of Negative Outcomes of Bone Metastases From Some Tumors
The skeleton is the most common site of tumor metastasis, and complications from bone metastases are a challenge in disease management. Biochemical markers of bone metabolism may be able to provide valuable insight into the development of skeletal complications. In a new study, Pierre Major, M.D., of the Juravinski Cancer Centre in Hamilton, Ontario, and colleagues looked at bone markers--N-telopeptide and bone-specific alkaline phosphatase--in patients with bone metastases secondary to prostate cancer, non–small-cell lung cancer, or other solid tumors who were assigned to the placebo group in two trials of zoledronic acid. High levels of each marker at the beginning of the study and recent marker levels were associated with negative clinical outcomes, including death, in these patients.
Contact: Roxanne Kantzavelos, Public Relations, Hamilton Health Sciences, McMaster University, 905-521-2100 x73058, kantzave@hhsc.ca
Also in the January 5 JNCI:
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oupjournals.org/.
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JNCI Journal of the National Cancer Institute