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DT-13 inhibits breast cancer cell migration via non-muscle myosin II-A regulation in tumor microenvironment synchronized adaptations

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Abstract

Background

Tumor metastasis is a terrifying characteristic of cancer. Numerous studies have been conducted to overcome metastasis by targeting tumor microenvironment (TME). However, due to complexity of tumor microenvironment, it remained difficult for accurate targeting. Dwarf-lillytruf tuber monomer-13 (DT-13) possess good potential against TME.

Objective

As TME is supportive for tumor metastasis, alternatively it is a challenging for therapeutic intervention. In our present study, we explored molecular mechanism through which TME induced cell migration and how DT-13 interferes in this mechanism.

Methods

We used a novel model of co-culture system which is eventually developed in our lab. Tumor cells were co-cultured with hypoxia induced cancer-associated fibroblasts (CAF) or with chemically induced cancer-associated adipocytes (CAA). The effect of hypoxia in conditioned medium for CAF was assessed through expression of α-SMA and HIF by western blotting while oil red staining was done to assess the successful chemical induction for adipocytes (CAA), the effect of TME through conditioned medium on cell migration was analyzed by trans-well cell migration, and cell motility (wound healing) analyses. The expression changes in cellular proteins were assessed through western blotting and immunofluorescent studies.

Results and conclusion

Our results showed that tumor microenvironment has a direct role in promoting breast cancer cell migration by stromal cells; moreover, we found that DT-13 restricts this TME regulated cell migration via targeting stromal cells in vitro. Additionally we also found that DT-13 targets NMII-A for its effect on breast cancer cell migration for the regulation of stromal cells in TME.

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Data availability

Supporting data on our present study can be made available on request.

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Acknowledgements

We highly acknowledge Higher Education Commission (HEC) of Pakistan for funding our research scholar Dr. Ghulam Jilany Khan for his studies in China Pharmaceutical University. We are highly thankful to Prof. Dr. Yu Boyang, School of Chinese Material Medicine, China Pharmaceutical University, for kindly providing us the drug (DT-13) with purity > 95% for the experimental purposes.

Funding

This study was financially supported by the National Natural Science Foundation of China (No. 81601034, No. 81102853, No. 81573456 and No. 81773766).

Author information

Author notes

  1. Y. Gao, G. J. Khan and X. Wei have contributed equally to this work.

Authors and Affiliations

  1. Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, 210009, China

    Y. Gao, G. J. Khan, X. Wei & L. Sun

  2. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, People’s Republic of China

    G. J. Khan

  3. Faculty of Pharmacy (FOP), University of Central Punjab, Lahore, Pakistan

    G. J. Khan

  4. Engineering Research Center of Natural Medicine and Functional Food, Institute of Pharmaceutical Biotechnology, School of Biological and Food Engineering, Suzhou University, 49, Bianhe Road, Suzhou, 234000, People’s Republic of China

    K.-F. Zhai

  5. Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    S. Yuan

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  1. Y. Gao
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Contributions

Dr. YingshengGao and Dr. Xiaohui Wei designed and performed the experimentation and figured out the findings. Dr. Ghulam Jilany Khan wrote the manuscript and designed/ arranged the data for manuscript writing and contributed equally with YingshengGao, and Xiaohui Wei; Dr. Ke-Feng Zhai arranged the data for manuscript publication and corresponded for the publication. Prof. Dr. Shengtao Yuan and Prof. Dr. Li Sun supervised the studies and guided for the experimentation theme of the study, designed the whole study plan, provided the resources for paper and are corresponding authors of this manuscript.

Corresponding authors

Correspondence to K.-F. Zhai, L. Sun or S. Yuan.

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Gao, Y., Khan, G.J., Wei, X. et al. DT-13 inhibits breast cancer cell migration via non-muscle myosin II-A regulation in tumor microenvironment synchronized adaptations. Clin Transl Oncol 22, 1591–1602 (2020). https://doi.org/10.1007/s12094-020-02303-z

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  • DOI: https://doi.org/10.1007/s12094-020-02303-z

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