open access

Vol 89, No 4 (2018)
Research paper
Published online: 2018-04-30
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Wound fluids collected from patients after IORT treatment activates extrinsic apoptotic pathway in MCF7 breast cancer cell line

Katarzyna Ida Kulcenty12, Igor Piotrowski12, Karolina Zaleska1, Dawid Murawa, Wiktoria Maria Suchorska12
·
Pubmed: 29781071
·
Ginekol Pol 2018;89(4):175-182.
Affiliations
  1. Radiobiology Labolatory, Department of Medical Physics, Greater Poland Cancer Centre, Garbary 15 Street, 61-866 Poznań, Poland
  2. Department of Electroradiology, University of Medical Sciences, Poznan, Poland, Garbary 15 Street, 61-866 Poznań, Poland

open access

Vol 89, No 4 (2018)
ORIGINAL PAPERS Gynecology
Published online: 2018-04-30

Abstract

Objectives: Intraoperative radiotherapy (IORT) relates to irradiation of diseased tissue during the surgery within the tumor bed. The reason for this process is based on the fact that the increase in the radiation dose increases local tumor control. It was shown that postoperative fluids obtained from patients after breast cancer conserving surgery, stimulated motility and invasiveness of tumor cells in vitro. The results obtained from TARGIT clinical trial demonstrated that IORT significantly inhibits the stimulatory effect of wound fluids on tumor cells in vitro. We therefore speculated that wound fluids collected from patients after IORT treatment may induce the apoptosis in breast cancer cell lines and it may be a reason for their lower proliferation rate and potential to metastasis.

Material and methods: Breast cancer MCF7 cell line was incubated with wound fluids collected from patients after conserving breast cancer surgery or surgery followed by IORT for 4 days. Then the expression of markers associated with extrinsic or intrinsic apoptosis pathway was established.

Results: Our results clearly indicate activation of extrinsic apoptosis pathway by wound fluids collected from patients after IORT treatment. No changes in apoptotic markers were seen in cells treated with wound fluids collected from patients after the surgery alone.

Conclusions: Thus we confirmed that wound fluids collected from patients after IORT treatment may induce the apoptosis in breast cancer cell lines and it may be a reason for their lower proliferation rate and invasiveness of tumor cells in vitro.

Abstract

Objectives: Intraoperative radiotherapy (IORT) relates to irradiation of diseased tissue during the surgery within the tumor bed. The reason for this process is based on the fact that the increase in the radiation dose increases local tumor control. It was shown that postoperative fluids obtained from patients after breast cancer conserving surgery, stimulated motility and invasiveness of tumor cells in vitro. The results obtained from TARGIT clinical trial demonstrated that IORT significantly inhibits the stimulatory effect of wound fluids on tumor cells in vitro. We therefore speculated that wound fluids collected from patients after IORT treatment may induce the apoptosis in breast cancer cell lines and it may be a reason for their lower proliferation rate and potential to metastasis.

Material and methods: Breast cancer MCF7 cell line was incubated with wound fluids collected from patients after conserving breast cancer surgery or surgery followed by IORT for 4 days. Then the expression of markers associated with extrinsic or intrinsic apoptosis pathway was established.

Results: Our results clearly indicate activation of extrinsic apoptosis pathway by wound fluids collected from patients after IORT treatment. No changes in apoptotic markers were seen in cells treated with wound fluids collected from patients after the surgery alone.

Conclusions: Thus we confirmed that wound fluids collected from patients after IORT treatment may induce the apoptosis in breast cancer cell lines and it may be a reason for their lower proliferation rate and invasiveness of tumor cells in vitro.

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Keywords

apoptosis, wound fluids, intraoperative radiation therapy, breast cancer

About this article
Title

Wound fluids collected from patients after IORT treatment activates extrinsic apoptotic pathway in MCF7 breast cancer cell line

Journal

Ginekologia Polska

Issue

Vol 89, No 4 (2018)

Article type

Research paper

Pages

175-182

Published online

2018-04-30

Page views

1444

Article views/downloads

1201

DOI

10.5603/GP.a2018.0030

Pubmed

29781071

Bibliographic record

Ginekol Pol 2018;89(4):175-182.

Keywords

apoptosis
wound fluids
intraoperative radiation therapy
breast cancer

Authors

Katarzyna Ida Kulcenty
Igor Piotrowski
Karolina Zaleska
Dawid Murawa
Wiktoria Maria Suchorska

References (37)
  1. Lipponen P, Aaltomaa S, Kosma VM, et al. Apoptosis in breast cancer as related to histopathological characteristics and prognosis. European Journal of Cancer. 1994; 30(14): 2068–2073.
  2. Wang D, Hu K, Gao N, et al. High throughput screening of cytokines, chemokines and matrix metalloproteinases in wound fluid induced by mammary surgery. Oncotarget. 2015; 6(30): 29296–29310.
  3. Demicheli R, Valagussa P, Bonadonna G. Does surgery modify growth kinetics of breast cancer micrometastases? Br J Cancer. 2001; 85(4): 490–492.
  4. Candido J, Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013; 33 Suppl 1: S79–S84.
  5. Benson JR, Jatoi I, Keisch M, et al. Early breast cancer. Lancet. 2009; 373(9673): 1463–1479.
  6. Piotrowski I, Kulcenty K, Wichtowski M, et al. Intraoperative Radiotherapy of Breast Cancer and Its Biological Effects. Breast Care (Basel). 2017; 12(2): 109–113.
  7. Belletti B, Vaidya JS, D'Andrea S, et al. Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res. 2008; 14(5): 1325–1332.
  8. Tagliabue E, Agresti R, Carcangiu ML, et al. Role of HER2 in wound-induced breast carcinoma proliferation. Lancet. 2003; 362(9383): 527–533.
  9. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer. 2003; 3(6): 453–458.
  10. Mothersill C, Seymour C. Radiation-induced bystander effects and adaptive responses--the Yin and Yang of low dose radiobiology? Mutat Res. 2004; 568(1): 121–128.
  11. Hengartner MO. The biochemistry of apoptosis. Nature. 2000; 407(6805): 770–776.
  12. Degterev A, Boyce M, Yuan J. A decade of caspases. Oncogene. 2003; 22(53): 8543–8567.
  13. Kaina B. DNA damage-triggered apoptosis: critical role of DNA repair, double-strand breaks, cell proliferation and signaling. Biochem Pharmacol. 2003; 66(8): 1547–1554.
  14. Zaleska K, Przybyła A, Kulcenty K, et al. Wound fluids affect miR-21, miR-155 and miR-221 expression in breast cancer cell lines, and this effect is partially abrogated by intraoperative radiation therapy treatment. Oncol Lett. 2017; 14(4): 4029–4036.
  15. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25(4): 402–408.
  16. Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer. 2002; 2(6): 420–430.
  17. Holmgren L, O'Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995; 1(2): 149–153.
  18. Veldwijk MR, Gerhardt A, Giordano FA, et al. Comparison of the proliferative and clonogenic growth capacity of wound fluid from breast cancer patients treated with and without intraoperative radiotherapy. Translational Cancer Research. 2015; 4: 173–177.
  19. Segatto I, Berton S, Sonego M, et al. Surgery-induced wound response promotes stem-like and tumor-initiating features of breast cancer cells, via STAT3 signaling. Oncotarget. 2014; 5(15): 6267–6279.
  20. Makin G, Dive C. Apoptosis and cancer chemotherapy. Trends in cell biology. 2001; 11: S22–26.
  21. Keane MM, Ettenberg SA, Nau MM, et al. Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. Cancer Res. 1999; 59(3): 734–741.
  22. Singh TR, Shankar S, Chen X, et al. Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. Cancer Res. 2003; 63(17): 5390–5400.
  23. Wang S, El-Deiry WS. TRAIL and apoptosis induction by TNF-family death receptors. Oncogene. 2003; 22(53): 8628–8633.
  24. Rahman M, Pumphrey JG, Lipkowitz S, et al. The TRAIL to targeted therapy of breast cancer. Adv Cancer Res. 2009; 103: 43–73.
  25. Ashkenazi A, Pai RC, Fong S, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999; 104(2): 155–162.
  26. Wang S, El-Deiry WS. Requirement of p53 targets in chemosensitization of colonic carcinoma to death ligand therapy. Proc Natl Acad Sci U S A. 2003; 100(25): 15095–15100.
  27. Chinnaiyan AM, Prasad U, Shankar S, et al. Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. Proc Natl Acad Sci U S A. 2000; 97(4): 1754–1759.
  28. Buchsbaum DJ, Zhou T, Grizzle WE, et al. Antitumor efficacy of TRA-8 anti-DR5 monoclonal antibody alone or in combination with chemotherapy and/or radiation therapy in a human breast cancer model. Clin Cancer Res. 2003; 9(10 Pt 1): 3731–3741.
  29. Lagadec C, Adriaenssens E, Toillon RA, et al. Tamoxifen and TRAIL synergistically induce apoptosis in breast cancer cells. Oncogene. 2008; 27(10): 1472–1477.
  30. Wagner JM, Hackanson B, Lübbert M, et al. Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin Epigenetics. 2010; 1(3-4): 117–136.
  31. Carew JS, Giles FJ, Nawrocki ST. Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy. Cancer Lett. 2008; 269(1): 7–17.
  32. Chinnaiyan P, Vallabhaneni G, Armstrong E, et al. Modulation of radiation response by histone deacetylase inhibition. Int J Radiat Oncol Biol Phys. 2005; 62(1): 223–229.
  33. Munshi A, Tanaka T, Hobbs ML, et al. Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of gamma-H2AX foci. Mol Cancer Ther. 2006; 5(8): 1967–1974.
  34. Munshi A, Kurland JF, Nishikawa T, et al. Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity. Clin Cancer Res. 2005; 11(13): 4912–4922.
  35. Chopin V, Slomianny C, Hondermarck H, et al. Synergistic induction of apoptosis in breast cancer cells by cotreatment with butyrate and TNF-alpha, TRAIL, or anti-Fas agonist antibody involves enhancement of death receptors' signaling and requires P21(waf1). Exp Cell Res. 2004; 298(2): 560–573.
  36. Singh TR, Shankar S, Srivastava RK. HDAC inhibitors enhance the apoptosis-inducing potential of TRAIL in breast carcinoma. Oncogene. 2005; 24(29): 4609–4623.
  37. Fulda S. Modulation of TRAIL-induced apoptosis by HDAC inhibitors. Curr Cancer Drug Targets. 2008; 8(2): 132–140.

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