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01.12.2018 | Letter to the Editor | Ausgabe 1/2018 Open Access

Journal of Hematology & Oncology 1/2018

Selective killing of circulating tumor cells prevents metastasis and extends survival

Zeitschrift:
Journal of Hematology & Oncology > Ausgabe 1/2018
Autoren:
Yi Rang Kim, Jung Ki Yoo, Chang Wook Jeong, Jin Woo Choi
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13045-018-0658-5) contains supplementary material, which is available to authorized users.
A correction to this article is available online at https://​doi.​org/​10.​1186/​s13045-018-0688-z.

Abstract

Distant metastasis is initiated by circulating tumor cells (CTCs), which are considered to be a determining factor for the degree of metastasis and the survival of cancer patients. Although CTC-based diagnostic approaches are being rapidly developed, limited studies have proven the benefits of CTC elimination, with most studies providing only hypothetical inference because of the technical difficulty in examining the effects of CTC elimination in vivo. We modified photodynamic therapy to specifically eliminate green fluorescent protein (GFP)-expressing CTCs and evaluated the therapeutic efficacy of CTC elimination. When circulating blood is illuminated with a blue laser (λ = 473 nm), the combination of GFP and photosensitizers induces a selective elimination of GFP-expressing CTCs, with limited effect on normal cells. In GFP-expressing cancer cell-infused or transplanted mice models, the treatment suppressed distant metastasis and extended the survival of the tumor-bearing mice. Taken together, CTCs are a core seed to be metastasized into secondary organs and elimination of CTCs may improve the survival of cancer patients.

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Zusatzmaterial
Additional file 1: Changes in colony formation according to the time elapsed since the intravenous injection of NCI-H460 cancer cells. a Change in colony formation according to the time elapsed since cancer cell injection. NCI-H460 cells (1 × 105) were intravenously injected into mice and whole blood was collected by cardiac puncture. After lysis of the red blood cells, 200 μL was spread onto a 35-mm dish and incubated for 7 days. The clone numbers were counted using crystal violet staining. The minutes represent the time passed between the cell injection and the blood collection. b The change in cancer cell colony number expressed as a graph. ns, not significant; **, P < 0.01. (PDF 45 kb)
13045_2018_658_MOESM1_ESM.pdf
Additional file 2: Clonogenic assay. a Clonogenic assay using whole blood taken after the experiment. b The images are close-ups of 1 and 2 indicated in C. GFP signal of each colony was confirmed. (PDF 50 kb)
13045_2018_658_MOESM2_ESM.pdf
Additional file 3: Monitoring of primary tumor growth in both the treated and untreated groups. ns, non-specific. (PDF 24 kb)
13045_2018_658_MOESM3_ESM.pdf
Additional file 4: Comparison of CTCs and CD45 positive leukocytes in treated and untreated mice. The fluorescent images of CTCs from treated and untreated mice were compared (left panel). Changes in CTC and leukocyte numbers were confirmed by performing EpCAM and CD45 immunostaining, respectively (middle and right panel). (PDF 26 kb)
13045_2018_658_MOESM4_ESM.pdf
Additional file 5: Effect of CTC-targeting PDT on hematologic profiles. After 2 weeks of treatment, the blood from four mice was taken and a complete blood count test was performed. The number of white blood cells (WBC), red blood cells (RBC), hemoglobin, and platelets were counted. The results were compared with those from four untreated control mice. ns, non-specific. (PDF 28 kb)
13045_2018_658_MOESM5_ESM.pdf
Additional file 6: Supplementary Materials and Methods. (DOCX 18 kb)
13045_2018_658_MOESM6_ESM.docx
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