Alteration of protein expression pattern of vascular endothelial growth factor (VEGF) from soluble to cell-associated isoform during tumourigenesis

Abstract

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells, and its expression has been correlated with increased tumour angiogenesis. Although numerous publications dealing with the measurement of circulating VEGF for diagnostic and therapeutic monitoring have been published, the relationship between the production of tissue VEGF and its concentration in blood is still unclear. The aims of this study were to determine: 1) The expression pattern of VEGF isoforms at the protein level in colorectal and lung adenocarcinoma in comparison to the pattern in corresponding adjacent normal tissues 2) The relationship between the expression pattern of VEGF and total level of circulating VEGF in the blood to clarify whether the results of measuring circulating VEGF can be used to predict VEGF expression in tumour tissues.</p> <p>Methods</p> <p>Ninety-four tissue samples were obtained from patients, 76 colorectal tumour tissues and 18 lung tumour tissues. VEGF protein expression pattern and total circulating VEGF were examined using western blot and capture ELISA, respectively.</p> <p>Results</p> <p>Three major protein bands were predominately detected in tumour samples with an apparent molecular mass under reducing conditions of 18, 23 and 26 kDa. The 18 kDa VEGF protein was expressed equally in both normal and colorectal tumour tissues and predominately expressed in normal tissues of lung, whereas the 23 and 26 kDa protein was only detected at higher levels in tumour tissues. The 18, 23 and 26 kDa proteins are believed to represent the VEGF₁₂₁, the VEGF₁₆₅and the VEGF₁₈₉, respectively. There was a significant correlation of the expression of VEGF₁₆₅with a smaller tumour size maximum diameter <5 cm (p < 0.05), and there was a significant correlation of VEGF₁₈₉with advanced clinical stage of colorectal tumours. The measurement of total circulating VEGF in serum revealed that cancer patients significantly (p < 0.001) possessed a higher level of circulating VEGF (1081 ± 652 pg/ml in colorectal and 1,251 ± 568 pg/ml in lung) than a healthy volunteer group (543 ± 344 pg/ml). No correlation between the level of circulating VEGF and the pathologic features of tumours was observed.</p> <p>Conclusion</p> <p>Our findings indicate that the expression patterns of VEGF isoforms are altered during tumourigenesis as certain isoform overexpression in tumour tissues correlated with tumour progression indicating their important role in tumour development. However, measurement of VEGF in the circulation as a prognostic marker needs to be carefully evaluated as the cell-associated isoform (VEGF₁₈₉), but not the soluble isoform (VEGF₁₂₁and VEGF₁₆₅) appears to play important role in tumour progression.</p

Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

“…The current results substantiate this hypothesis, and furthermore, suggest that VEGF188 expression is uniquely predictive of treatment outcome. Interestingly, several studies have suggested that VEGF189 expression in human cancers is associated with tumor progression and poor outcome from conventional treatments (47)(48)(49)(50).…”

The importance of −460 C/T and +405 G/C single nucleotide polymorphisms to the function of vascular endothelial growth factor A in colorectal cancer

“…VEGF-A 189 is completely sequestered in the ECM but may be released in a diVusible form after enzymatic cleavage (Houck et al 1992;Park et al 1993). Finally, VEGF-A 189 may be associated with an increased risk of metastatic spread (Cressey et al 2005;Tokunaga et al 1998). The relative expression of these isoforms in CRC compared to normal colonic tissues needs to be investigated along with the possible inXuence of the SNPs.…”

Serum vascular endothelial growth factor and angiogenesis are related to the prognosis of patients with gastrointestinal stromal tumors

“…Although many studies have found that the SVEGF level in patients with cancer is an indicator of angiogenesis, the relationship between VEGF expression and SVEGF concentration is still unclear. VEGF levels in gastric cancer patients were significantly higher than those in healthy controls, and MVD was significantly correlated with both tumor VEGF expression and serum VEGF level [25,26]. It was reported that SVEGF in colorectal cancer patients was higher than in healthy volunteers, but there was no correlation between the level of SVEGF and the pathologic features of tumors [26,27].…”

“…Recently, studies showed that vascularity is a prognostic factor for some malignant tumors, and that CD31 staining can be used to assess tumor vascularity which is expressed as microvessel density (MVD) [7][8][9]. The level of serum VEGF (SVEGF) is higher in many cancers than in healthy controls and has recently been found to provide a way to estimate the expression of VEGF in many cancers [10][11][12]. Roumen et al [13] found no significant difference in SVEGF levels between colorectal cancer patients and controls.…”