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What Do You know about Vascular Endothelial Growth Factor in Cancer Diagnosis?



What is VEGF?

Vascular endothelial growth factor (VEGF) is a potent glycoprotein with various biological functions. As an endothelial cell-specific mitogen, VEGF plays a critical role in regulating vascular endothelial cells' proliferation, migration, and lumen formation, participating in angiogenesis, and increasing blood capillary permeability. In addition to endothelial cells, VEGF is also expressed in many other cell types including tumor cells. The up-regulation of VEGF in tumors will lead to tumor angiogenesis and dampen the delivery of anti-tumor drugs into tumor tissue.


Dr. Judah Folkman, the founder of the VEGF theory and a pioneer in tumor research, proposed his Folkman theory that in the absence of new angiogenesis, solid tumors have to compete with their surrounding cells to obtain extra oxygen and nutrients, and the limited resources make the tumor tissue hard to grow exceeding 1~2 mm3. If the size of tumor tissue is more extensive than 2~3 mm3, they must rely on angiogenesis to provide sufficient oxygen and nutrients to maintain their rapid growth. A large number of studies on VEGF and tumor diagnosis have demonstrated the elevated VEGF levels in cancer patients' blood samples, suggesting that VEGF is a promising tumor marker. To date, VEGF has been broadly used for tumor screening and auxiliary diagnosis, as well as the evaluation of cancer treatment and prognosis.


The correlation between tumor and blood vessel growth

A tumor is a mass of abnormal cells. To grow and survive, cells of the human body must be nourished by blood, which provides oxygen and various nutrients. Impressively, blood vessels of various sizes can be seen everywhere on the surface and in the depths of tumors, and the nutrients of life are continuously supplied to the depths of tumor cells through these blood vessels. Meanwhile, along with the rapid growth of a tumor, the nearby blood vessels are also wildly developing, and these new capillaries grow as disorderly as the tumor.


Being the essential regulator of angiogenesis, the human VEGF protein was initially purified and identified by scientists from two biotechnology companies in the United States in 1989, and its gene sequence was cloned and determined after that. VEGF has multiple isoforms, and molecular weight ranges from 35 to 44 kDa. Each isoform binds to its corresponding receptor(s) (vascular endothelial growth factor receptor, VEGFR) to regulate blood vessel formation. In 2004, the world's first humanized monoclonal antibody, Avastin, targeting VEGF for clinical treatment of tumors was approved in the United States.


VEGF in tumor screening

Cancer patients diagnosed in their middle and late stages have a lower chance of survival, more significant problems associated with treatment, and higher care costs. Therefore, early screening of suspicious or asymptomatic patients is critical to improve the survival rate and prolong the survival time of cancer patients. Given that VEGF begins to be produced in large amounts during the early stage of cell transformation such as the Tis stage and T1 stage, the ideal time window for tumor screening, the diagnosed patients according to VEGF will have the best chance for successful treatment. 


Almost all cancers are positively correlated with VEGF concentrations at early stages. When the concentration of VEGF is low at the normal range, tumor lesions are generally unable to develop new blood vessels, and in turn, the tumor will be maintained at a diameter of 1-2 mm, which is almost harmless to health and is easily eliminated by the human immune system. Once angiogenesis is present, the tumor overgrows, followed by its malignant features. Being a key regulator in promoting angiogenesis, VEGF has been considered an early warning indicator for cancer risk. Of note, cancer in vitro diagnosis (IVD) by detecting VEGF is very sensitive. VEGF will not show "negative" due to changes in the biological properties of tumors. In other words, regardless of primary tumor or tumors of recurrence and metastasis, as long as the tumor has a growth trend, it will be reflected in VEGF. This property also makes VEGF an excellent biomarker to evaluate the efficacy of cancer treatment, such as tumor surgery, radiotherapy, and chemotherapy. 


Of course, the factors that may lead to the increase of VEGF concentration are not only cancer but also normal physiological phenomena such as women's menstrual period and some other diseases, such as rheumatoid, diabetic retinopathy, active tuberculosis, psoriasis, and so on. Therefore, don't be nervous when the VEGF index is abnormal. You can review it at intervals, follow up to observe the dynamic change data, and if necessary, go to a medical institution for further inspection to clarify the cause. 

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