Acute phase response induction by cancer treatment with photodynamic therapy

Abstract

Inflammation and immunity development are well recognized as responses to tumor treatment by photodynamic therapy (PDT). To demonstrate that another major host response effector process, acute phase response, may be also induced by this cancer treatment modality, the expression of serum amyloid P component (SAP) acknowledged as a hallmark acute phase reactant in the mouse was investigated following PDT of murine FsaR fibrosarcomas. The results reveal almost 150-fold increase in the expression of SAP gene in the liver of mice bearing tumors treated by Photofrin-mediated PDT, while serum SAP levels increased around 50-fold at the peak interval about 24 hr post PDT. The same tumor treatment induced also the liver gene upregulation and serum levels elevation of another established acute phase reactant, mannose-binding lectin A (MBL-A). Both SAP and MBL-A were found to accumulate in PDT-treated tumors, but this includes local production because their genes in these tumor tissues were upregulated as well. Gene encoding C-reactive protein (CRP) was also upregulated almost 7-fold in the same tumor tissues, suggesting a rare example of CRP participation in host response of the mouse. Interleukin-6 and glucocorticoid hormones were identified as major mediators promoting tumor PDT-induced upregulation of liver SAP gene. Moreover, glucocorticoids were found to act as critical inducers of SAP gene upregulation in PDT-treated tumors. The study definitely proves the occurrence of a strong acute phase response following tumor PDT, and reveals that glucocorticoid hormones released during this development impact the expression of host response-relevant genes in PDT-treated tumors.