Characterization of Ovarian Tumor Vascular Cells, a New Source for Ovarian Cancer Biomarkers
26 Mar, 2007 11:36 am
We recently characterized the genes expressed by ovarian tumor blood vessel cells. This work demonstrated that the blood vessel cells in ovarian cancer are different from normal blood vessel cells found in healthy ovary. Ovarian tumor vessels express numerous proteins that are not identified, or are expressed at significantly lower levels, in healthy ovary. These markers demonstrated quantitative differences in expression when tested in tumor endothelial cells from different tumor types inlcuding, ovarian cancer, lung cancer and melanoma suggesting that the tumor microenvironment may play a role in determining tumor vascular phenotype.
Importantly, researchers from M.D. Anderson have recently reported similar study of ovarian tumor blood vessels cells4. While this group used a different technique to isolate the tumor and normal vascular ovary cells, there was a significant overlap in the tumor vascular markers reported by the two independent studies. Such an overlap of results in array based studies is often rare, and confirms the robustness of the findings. These studies have therefore independently validated these ovarian tumor vascular specific markers.
While much work remains to be done, these ovarian tumor vascular markers have a significant potential for impact in the clinic. Since these biomarkers are expressed on the tumor vasculature and exposed to blood, they may be shed into the peripheral circulation. In order to grow larger than a few millimeters, tumors need to grow new blood vessels, thus these biomarkers may be shed into the blood early in the course of the disease. Detection of these proteins in the blood of patients may therefore aid in the early screening and diagnosis of ovarian cancer. As a proof of this principle, we demonstrated that one of these biomarkers, DR6, is elevated in the sera of ovarian cancer patients compared to healthy donors.
In addition to a potential role as biomarkers, these tumor vascular specific proteins also represent ideal targets for tumor specific therapeutics. The ability to effectively target tumor blood vessels and prevent their growth has proven an effective means to restrict tumor growth. We are beginning to develop antibodies to target specific tumor vascular proteins. Antibodies or drugs that would bind specifically to the tumor blood vessels could deliver high doses of anti-tumor therapy directly to the tumor environment. Tumor vessel targeted therapy could impact both tumor blood vessel growth and cancer cell growth with a single therapy. This combination of anti-blood vessel and anti-tumor therapy has proven a powerful combination in other tumor types. In addition, in theory, therapeutics targeting tumor vascular specific proteins should have few side effects, as they would not target healthy tissues.
Thus these two studies taken together are a step forward for ovarian cancer research. While much needs to be done, this work opens the door for potential new screening tools, diagnostic and therapeutic tools.
 Buckanovich RJ, Sasaroli D, O Brien-Jenkins A, et al. Tumor Vascular Proteins as Biomarkers in Ovarian Cancer Journal of Clinical Oncology 2007;25 (7):852-61.
 Lu C, Bonome T, Li Y, et al. Gene alterations identified by expression profiling in tumor-associated endothelial cells from invasive ovarian carcinoma. Cancer Research 2007;67(4):1757-68.