Vascular endothelial growth factor-A and changes in a tumor-bearing mouse model with Lewis lung cancer

Abstract

Abstract. Vascular endothelial growth factor-A (VEGF-A)affects tumor growth and metastasis through stimulation of angiogenesis. The purpose of this study was to describe features of Lewis lung cancer (LLC) in mice and compare the serum VEGF-A levels with those of normal control mice. Two groups of mice were compared: one was subcutaneously injected with LLC cells (n=16) and the other served as the normal control (n=6). The serum VEGF-A levels were measured by ELISA prior to inoculation, and at 7, 21 and 35 days post-inoculation. The tumor weight and the metastatic condition were evaluated on day 35. Changes in body weight and serum VEGF-A concentration over a period of time were compared between the groups using generalized estimating equations. The relationship between the primary tumor and the metastatic condition was analyzed using the Spearman's rank correlation test. The survival rate was 56.3% on day 35 post-tumor inoculation. No difference was found between the groups with regard to gastrocnemius muscle weight on day 35 post-inoculation [0.1315±0.0066 g vs. 0.1308±0.0069 g (normal control)]. In tumor-bearing mice, the weight gain at sacrifice was less (0.24±0.45 vs. 1.93±0.47 g, P= 0.01), the final mean tumor volume and weight were 4264.69±1038.32 mm 3 and 3.70±0.83 g, the number of nodules in the lungs and livers was 6.33 (range 0-20) and 2.22 (range 0-11), respectively, and the serum VEGF-A levels were significantly higher than those of control mice. In conclusion, lower body weight gain, metastasis in the liver and lungs, and elevated VEGF-A levels are features of LLC in mice.

Endothelial Rac1 is essential for hematogenous metastasis to the lung

“…In the present study, we identified that LLC-secreted VEGF functions as a vasoactive factor that is able to induce the permeability through Rac1. Serum murine VEGF (mVEGF) levels were increased to 0.1 ng/ml in mice bearing LLC xenografts, this value is completely consistent with the literature that has also shown the serum levels of VEGF in mice bearing LLC xenografts [ 17 ], however, in our in vitro experiments, we activated Rac1 in HUVEC in response to recombinant human VEGF-A (rhVEGF-A) at 50 ng/ml that is much greater than serum mVEGF levels of mice bearing either LLC xenografts or hematogenously metastatic LLC. We suggest that the bioactivity of circulating mVEGF is equivalent to that of in vitro rhVEGF-A in induction of endothelial Rac1 activation.…”

Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma

“…Tumor angiogenesis, the formation of new blood vessels from endothelial precursors within tumors, is a prerequisite step for growth and progression of solid malignancies [ 6 ]. Vascular endothelial growth factor (VEGF) is an essential player in tumor angiogenesis and mediates tumor aggressiveness [ 7 - 9 ]. Monocyte chemotactic protein-1 (MCP-1), a key CC chemokine responsible for trafficking and activation of monocytes/macrophages has been recognized as an important angiogenic chemokine [ 10 , 11 ]; it also plays a critical role in solid tumors [ 12 ].…”

Mesenchymal Stem Cells Promote Metastasis of Lung Cancer Cells by Downregulating Systemic Antitumor Immune Response

“…Experimental metastases were induced by intravenous injection of 5 × 10 4 LLC1 cells [ 10 ]. Mice intravenously received either 5 × 10 5 MSCs or saline one week after injection of LLC1 cells.…”