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

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.

Automated summary

This study investigated the impact of CCH treatment on breast cancer cells. The results showed that CCH had an effect on the proliferation and wound healing of breast cancer cells in vitro and in vivo, but did not significantly change the cell cycle and apoptosis. No evidence of metastasis was observed in the in vivo experiments, and no relevant alterations in metastasis-related genes were detected. Therefore, CCH does not have an impact on tumor growth or metastasis formation.