Dying cells program their expedient disposal: serum amyloid P component upregulation in vivo and in vitro induced by photodynamic therapy of cancer.
Serum amyloid P component (SAP) is known as a prototypic acute phase reactant in the mouse and the protein that binds to dying cells securing their swift disposal by phagocytes. Treatment of solid tumors by photodynamic therapy (PDT) triggers SAP production in the liver of host mice, its release in the circulation and accumulation in PDT-targeted lesions. In the present study, mouse Lewis lung carcinoma (LLC) cells treated in vitro by PDT are shown to upregulate their gene encoding SAP. This effect was manifested following PDT treatment mediated by various types of photosensitizers (Photofrin, BPD, mTHPC, ALA). Generated SAP protein was not detected in tissue supernatants but remained localized to producing PDT-treated cells. The upregulation of SAP gene was observed also in untreated IC-21 macrophages after they were co-incubated for 4 h with PDT-treated LLC cells. Based on these findings, SAP that accumulates in PDT-treated tumors may originate from both systemic sources (released from the liver as acute phase reactant) and local sources; the latter could include tumor cells directly sustaining PDT injury and macrophages invading the tumor that become stimulated by signals from these affected tumor cells. Since SAP gene upregulation in LLC cells increased with the lethality of PDT dose used for their treatment, we propose that cells sensing they are inflicted with mortal injury can turn on molecular programs insuring not only that they die an innocuous form of death (apoptosis) but also that once they are dead their elimination is (facilitated by SAP) swift and efficient.
Merchant
Soroush
S
British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, B.C., Canada.
Sun
Jinghai
J
Korbelik
Mladen
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010778:Photochemotherapy; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000528:radiation effects*
D000683:Serum Amyloid P-Component