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The collagenase of the bacterium Clostridium histolyticum does not favor metastasis of breast cancer

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Abstract

Background

Breast cancer is the most common malignancy among women worldwide. As survival rates increase, breast reconstruction and quality of life gain importance. Of all women undergoing breast reconstruction, approximately, 70% opt for silicone implants and 50% of those develop capsular contracture, the most prevalent long-term complication. The collagenase of the bacterium Clostridium histolyticum (CCH) showed promising results in the therapy of capsule contracture; however, its influence on residual cancer cells is unknown. The aim of this study was to investigate whether CCH-treatment negatively impacts breast cancer cells in vitro and in vivo.

Methods

MDA-MB-231 and MCF-7 cells were used in this study. In vitro, we tested the influence of CCH on proliferation, wound healing, migration and cell cycle by MTT-assay, scratch-assay, transwell-migration-assay, and flow cytometry.

In vivo, solid tumors were induced in immune-deficient mice. CCH was injected into the tumors and tumor growth and metastasis formation was monitored by caliper measurement, in vivo bioluminescence imaging and histology. Gene expression analysis was performed by microarray including 27,190 genes.

Results

CCH-incubation led to a dose-dependent reduction in proliferation for both cell lines, while wound healing was reduced only in MDA-MB-231 cells. No morphological alterations were monitored in cell cycle or apoptosis. In vivo, bioluminescence imaging and histology did not show any evidence of metastasis. Although CCH led to changes in gene expression of breast cancer cells, no relevant alterations in metastasis-related genes were monitored.

Conclusion

CCH has no impact on tumor growth or metastasis formation in vitro and in vivo. This paves the way for first clinical trials.

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Acknowledgements

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Authors and Affiliations

  1. Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany

    Yannick Fabian Diehm, Katharina Marstaller, Anna-Maria Seckler, Julia Thomé, Dimitra Kotsougiani-Fischer, Ulrich Kneser & Sebastian Fischer

  2. Toxicology and Chemotherapy Unit, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Katharina Marstaller, Anna-Maria Seckler, Martin Reinhold Berger & Michael Zepp

  3. Institute of Pathology, University Medical Center, Johannes-Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany

    Matthias Martin Gaida

Authors
  1. Yannick Fabian Diehm
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  2. Katharina Marstaller
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  3. Anna-Maria Seckler
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  4. Martin Reinhold Berger
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  9. Ulrich Kneser
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  10. Sebastian Fischer
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Contributions

All the authors contributed to the study conception and design. Methodology: YFD, KM, AMS, JT, MZ, MMG, and SF. Formal analysis and investigation: YFD, MRB, UK, and SF. Writing—original draft preparation: YFD, DKF, and SF. Writing—review and editing: all the authors. Supervision: MRB, UK, and SF.

Corresponding author

Correspondence to Sebastian Fischer.

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Conflict of interest

The authors received funding support through an Educational Research Grant from Endo Pharmaceuticals (Malvern, USA). This grant was used to purchase general lab supply, both breast cancer cell lines, assays and immune-deficient mice. None of the authors received a salary for this study or has any financial interest.

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All applicable national and institutional guidelines for the care and use of animals were followed.

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Diehm, Y.F., Marstaller, K., Seckler, AM. et al. The collagenase of the bacterium Clostridium histolyticum does not favor metastasis of breast cancer. Breast Cancer 29, 599–609 (2022). https://doi.org/10.1007/s12282-022-01337-1

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  • DOI: https://doi.org/10.1007/s12282-022-01337-1

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