Abstract
In pituitary adenomas, which are known to display decreased vascular density in comparison to normal pituitary tissue, the exact role of angiogenesis in tumor transformation and progression remains unclear. As recent studies have shown that patients with pituitary adenomas display elevated inflammatory markers such as IL-8 and TNF-α, we have conducted initial investigations to further clarify the possibility of inflammation-induced angiogenesis in pituitary adenomas. To further explore these mechanisms, the murine folliculo-stellate-like TtT/GF cell line and human pituitary adenoma primary cell cultures were treated with the TLR-4 ligand LPS under basal and hypoxia-mimicking conditions (CoCl 2 treatment). HIF-1α and NF-κB expression was then studied by Western Immunoblotting. VEGF-A and IL-8/KC were measured by ELISA. Additional CD-31 immunohistochemistry of vessel density was performed. Finally, RT-PCR was conducted to verify the presence of TLR-4 and IL-8 receptors in human tumors. We observed that both LPS and CoCl 2 treatment strongly induce HIF-1α and NF-kB protein expression as well as VEGF-A and IL-8/KC secretion in all cell populations studied, suggesting possible crosstalk mechanisms. An interesting dichotomy of the angiogenic response (VEGF-A and IL-8 production) within tumor subtypes following LPS stimulation was observed, suggesting possible tumor-specific mechanisms of inflammatory responses. These results suggest that inflammation may play a role in angiogenesis in pituitary tumors. This not only provides the basis for further investigation of inflammation-induced angiogenesis, but also provides insight into the mechanisms of angiogenesis in pituitary adenomas in general, which when further understood may provide improved options for treatment and prevention.
Published Version
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