British Columbia Cancer Agency , Vancouver, BC , Canada.
Vilnius University Institute of Biotechnology , Vilnius , Lithuania.
Front Oncol. 2015 Feb 3;5:15. doi: 10.3389/fonc.2015.00015. eCollection 2015.
Calreticulin is recognized as one of the pivotal damage-associated molecular pattern molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT). The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse) was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT-vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT-vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor response elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.
钙网织蛋白被认为是关键的损伤相关分子模式分子之一，它能提醒宿主存在受损细胞。在这种作用下，钙网织蛋白会在接受多种癌症治疗（包括光动力疗法（PDT））的肿瘤细胞表面暴露。本研究的目的是研究外源性钙网织蛋白在增强 PDT 介导的抗肿瘤作用中的潜力。研究发现，重组钙网织蛋白与接受 PDT 治疗的小鼠 SCCVII 肿瘤细胞结合。与单独 PDT 相比，当在 PDT 后立即在肿瘤周围注射 0.4mg/mouse 的钙网织蛋白时，在免疫功能正常的 C3H/HeN 小鼠中生长的 SCCVII 肿瘤的治愈率得到提高。在免疫缺陷 NOD-scid 小鼠中生长的 SCCVII 肿瘤中，未获得 PDT 联合钙网织蛋白的治疗增益。在 PDT 疫苗方案中，将接受 PDT 治疗的 SCCVII 细胞用于接种 SCCVII 荷瘤小鼠，在注射前向细胞中添加重组钙网织蛋白可产生更好的治疗效果。在接受 PDT 治疗的细胞中，钙网织蛋白基因的表达减少，而在接受 PDT 疫苗治疗的小鼠的肿瘤、肝脏和脾脏组织中，该基因的表达没有变化。这些发现表明，外源性重组钙网织蛋白可以增强 PDT 或 PDT 生成的疫苗引发的抗肿瘤反应，因此可以作为 PDT 及可能其他诱导癌细胞应激治疗方式的有效佐剂。
