title: Involvement of damage-associated molecular patterns in tumor response to photodynamic therapy: surface expression of calreticulin and high-mobility group box-1 release.
abstract: Damage-associated molecular patterns (DAMPs), danger signal molecules expressed after injury or infection, have become recognized as prerequisite for orchestrating effective anti-tumor host response. The expression of two prototypical DAMPs, calreticulin and high-mobility group box-1 (HMGB1) protein, was examined following Photofrin-photodynamic therapy (PDT) of Lewis lung carcinoma (LLC) cells in vitro and LLC tumors growing in syngeneic mice. Cell surface expression of calreticulin was found to be highly increased at 1 h after PDT treatment both in vitro and in vivo. Increased exposure of calreticulin was also detected on the surface of macrophages from PDT-treated LLC tumors. At the same time interval, a rise in serum HMGB1 was detected in host mice. Intracellular staining of macrophages co-incubated for 16 h with PDT-treated LLC cells revealed elevated levels of HMGB1 in these cells. The knowledge of the involvement of these DAMPs uncovers important mechanistic insights into the development of host response induced by PDT.
authors.affiliation: British Columbia Cancer Research Centre, British Columbia Cancer Agency, 675 West 10th Avenue, Room 6.112, Vancouver, BC V5Z 1L3, Canada. mkorbelik@bccrc.ca
authors.forename: Mladen
authors.initials: M
authors.lastname: Korbelik
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Soroush
authors.initials: S
authors.lastname: Merchant
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000628:therapy; D002469:Cell Separation; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology
chemical_list: D037282:Calreticulin; D024243:HMGB1 Protein; D017319:Photosensitizing Agents; D017323:Dihematoporphyrin Ether