Expression of complement and pentraxin proteins in acute phase response elicited by tumor photodynamic therapy: The engagement of adrenal hormones

Treatment of solid tumors by photodynamic therapy (PDT) was recently shown to trigger a strong acute phase response. Using the mouse Lewis lung carcinoma (LLC) model, the present study examined complement and pentraxin proteins as PDT-induced acute phase reactants. The results show a distinct pattern of changes in the expression of genes encoding these proteins in the tumor, as well as host liver and spleen, following PDT mediated by photosensitizer Photofrin™. These changes were influenced by glucocorticoid hormones, as evidenced by transcriptional activation of glucocorticoid receptor and the upregulation of gene encoding this receptor. The expression of gene for glucocorticoid-induced zipper (GILZ) protein, whose activity is particularly susceptible to glucocorticoid regulation, was also changed in PDT-treated tumors. A direct demonstration that tumor PDT induces glucocorticoid hormone upregulation is provided by documenting elevated levels of serum corticosterone in mice bearing PDT-treated LLC tumors. Tumor response to PDT was negatively affected by blocking glucocorticoid receptor activity, which suggests that glucocorticoid hormones have a positive impact on the therapeutic outcome with this therapy.

Research highlights
► The expression of complement and pentraxin proteins is altered (upregulated in most cases) in mice bearing tumors treated by photodynamic therapy (PDT) due to the induction of acute phase response.
► It is demonstrated for the first time that tumor PDT induces a hormonal response involving adrenal glucocorticoids.
► Although the engaged adrenal hormones have potential to influence a wide variety of host response elements, these hormones have an overall positive impact on the outcome of tumor therapy with PDT.