Different Mechanisms Lead to the Angiogenic Process Induced by Three Adenocarcinoma Cell Lines

Abstract

Neoangiogenesis is essential for tumor and metastasis growth, but this complex process does not follow the same activation pathway, at least in tumor cell lines originated from different murine mammary adenocarcinomas. LMM3 cells were the most potent to stimulate new blood vessel formation. This response was significantly reduced by preincubating cells with indomethacin and NS-398, non-selective cyclooxygenase (COX) and COX-2 selective inhibitors, respectively. COX-1 and COX-2 isoenzymes were both highly expressed in LMM3 cells, and we observed that indomethacin was more effective than NS-398 to inhibit prostaglandin E2 (PGE2) synthesis. In addition, nitric oxide synthase (NOS) inhibitors, Nomega monomethyl L-arginine and aminoguanidine, also reduced LMM3-induced angiogenesis and nitric oxide (NO) synthesis as well. NOS2 > NOS3 proteins and arginase II isoform were detected in LMM3 cells by Western blot. The latter enzyme was also involved in the LMM3 neovascular response, since the arginase inhibitor, Nomega hydroxy L-arginine reduced the angiogenic cascade. On the other hand, parental LM3 cells were able to stimulate neovascularization via COX-1 and arginase products since only indomethacin and Nomega hydroxy L-arginine, which diminished PGE2 and urea synthesis, respectively, also reduced angiogenesis. In turn, LM2 cells angiogenic response could be due in fact to PGE2-induced VEGF liberation that stimulated neoangiogenesis at very low levels of NO.

Diagnosis of Suspicious Thyroid Nodules Using Four Protein Biomarkers

“…The function of ARG2 is not fully understood, but high levels of ARG2 have been described in tumors and cell lines (27,28). ARG2 was recently found overexpressed in cell lines derived from spontaneous murine mammary tumor and pulmonary metastases, and the authors suggested that ARG2 play a major role in tumor angiogenesis (29). These findings and the fact the ARG2 was found among the up-regulated tumor-related genes identified in a mice model that spontaneously develop FTC through progression of hyperplasia, capsular and vascular invasion, anaplasia, and eventually metastasis to distant organs (30) suggest that ARG2 may play a role in carcinogenesis.…”

Cyclooxygenase inhibition in early onset of tumor growth and related angiogenesis evaluated in EP1 and EP3 knockout tumor-bearing mice

“…Some studies report that NSAIDs seem to act directly on tumor cells with only minor effects on surrounding endothelial cells [26,27], while others put forward direct and main effects on the angiogenic process itself [28], similarly as seen in normal wound healing [29À32]. Also, various tumor cell lines seem to exert different effects on unanimous experimental conditions [33]. and in vivo, but host cells do also contribute to high circulating serum levels of PGE2 in mice with large tumor burden [14].…”

Lipoxygenase Pathway of Arachidonic Acid Metabolism in Growth Control of Tumor Cells of Different Type

“…PGE 2 can induce and mediate expression of some oncogenes [25,26], display a strong immunosuppressive effect [27], and it is an important factor for angiogenesis [28,29], growth [7 9], and metastasizing [30] of tumors. On the other hand, some oncogenes, chemical carcinogens, promot ers, and various factors essential for carcinogenesis are inducers of COX and, as a consequence, the biosynthesis of PGE 2 [2,3,31].…”