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Involvement of damage-associated molecular patterns in tumor response to photodynamic therapy: surface expression of calreticulin and high-mobility group box-1 release

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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.

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Acknowledgments

Denise McDougal provided expert assistance in flow cytometry. Axcan Pharma Inc. has provided Photofrin™ for this study.

Conflict of interest

The authors declare to have no conflict of interest in any form with respect to this article.

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Authors and Affiliations

  1. British Columbia Cancer Research Centre, British Columbia Cancer Agency, 675 West 10th Avenue, Room 6.112, Vancouver, BC, V5Z 1L3, Canada

    Mladen Korbelik, Wei Zhang & Soroush Merchant

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  1. Mladen Korbelik
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  2. Wei Zhang
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  3. Soroush Merchant
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Correspondence to Mladen Korbelik.

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Korbelik, M., Zhang, W. & Merchant, S. Involvement of damage-associated molecular patterns in tumor response to photodynamic therapy: surface expression of calreticulin and high-mobility group box-1 release. Cancer Immunol Immunother 60, 1431–1437 (2011). https://doi.org/10.1007/s00262-011-1047-x

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