Vascular Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a homodimeric 34 to 45 kilodalton, heparin-binding glycoprotein. VEGF has potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells.^1,2 VEGF expression is regulated by hypoxia, with levels increasing when cells detect an environment low in oxygen. Physiologically, VEGF induces new blood vessel formation during embryonic development, after tissue injury and in response to blocked vessels. VEGF is thought to play an important role in several physiologic processes, including wound healing, ovulation, menstruation, maintenance of blood pressure and pregnancy.¹ VEGF has also been associated with a number of pathologic processes that involve angiogenesis, including arthritis, psoriasis, macular degeneration and diabetic retinopathy.^1,3

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder, which is most commonly lambda restricted.⁴ The neurological hallmark, which forms one of the mandatory criteria for diagnosis, is a subacute onset demyelinating neuropathy, which can be rapidly disabling and painful. Elevated VEGF is highly specific for POEMS syndrome (though not pathognomonic) and thought to be involved in the pathophysiology of systemic features including organomegaly and volume overload. VEGF levels reflect disease activity, falling with treatment and rising with disease progression or relapse. Monitoring VEGF levels may be useful as a disease prognostic marker.⁵

In general, the growth and spread of tumors has been shown to be dependent on the development of increased vascularization in the tumor vicinity in order to maintain sufficient oxygenation.^1,6 Tumor expression of proangiogenic factors, including VEGF, has been associated with advanced tumor progression in a number of human cancers.^7,8 Increased expression of VEGF has been associated with poorer prognosis in patients with cancer of the colon,^9-11 stomach,^12-14 pancreas,^15,16 breast,^17-20 ovary,^21,22 prostate,^23,24 liver,²⁵ oral squamous cell,²⁶ bone²⁷ and in melanoma.²⁸ Serum VEGF levels are significantly higher than plasma levels. This is thought to reflect the fact that VEGF is released into the serum from platelets as part of the clotting process.²⁹ It has been hypothesized that VEGF released from activated platelets may have a role in angiogenesis during wound healing and may also be associated with pathological conditions, such as atherosclerosis, tumor growth and metastasis formation.²⁹ In different studies, serum VEGF^{12,21,22,25,26} and plasma VEGF^11,17,23,24 levels have been found to correlate with the clinical status of patients with cancer.