Yannick Fabian Diehm1, Katharina Marstaller1,2, Anna-Maria Seckler1,2, Martin Reinhold Berger2, Michael Zepp2, Matthias Martin Gaida3, Julia Thomé1, Dimitra Kotsougiani-Fischer1, Ulrich Kneser1, Sebastian Fischer4. 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. 2. Toxicology and Chemotherapy Unit, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. 3. Institute of Pathology, University Medical Center, Johannes-Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. 4. Department of Hand-, Plastic and Reconstructive Surgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 13, 67071, Ludwigshafen, Germany. sfischer@hotmail.de.
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.
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.
Authors: Yannick F Diehm; Christoph Hirche; Martin R Berger; Jörg Heil; Michael Golatta; Dimitra Kotsougiani; Bohdan Pomahac; Ulrich Kneser; Sebastian Fischer Journal: Aesthetic Plast Surg Date: 2018-11-19 Impact factor: 2.326
Authors: Sebastian Fischer; Yannick Diehm; Thomas Henzler; Martin R Berger; Jonas Kolbenschlag; Anne Latz; Ericka M Bueno; Christoph Hirche; Ulrich Kneser; Bohdan Pomahac Journal: Aesthetic Plast Surg Date: 2016-12-23 Impact factor: 2.326
Authors: Sebastian Fischer; Christoph Hirche; Yannick Diehm; Kristo Nuutila; Jurij Kiefer; Emre Gazyakan; Ericka M Bueno; Thomas Kremer; Ulrich Kneser; Bohdan Pomahac Journal: PLoS One Date: 2016-05-27 Impact factor: 3.240