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Breast Cancer: Proteolysis and Migration

  • Kingsley O. Osuala
  • Kyungmin Ji
  • Raymond R. Mattingly
  • Bonnie F. Sloane
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1152)

Abstract

Understanding breast cancer cell proteolysis and migration is crucial for developing novel therapies to prevent local and distant metastases. Human cancer cells utilize many biological functions comparable to those observed during embryogenesis conferring the cancer cells with survival advantages. One such advantage is the ability to secrete proteases into the tumor microenvironment in order to remodel the extracellular matrix to facilitate migration. These proteases degrade the extracellular matrix, which initially functions as a barrier to cancer cell escape from their site of origin. The extracellular matrix also functions as a reservoir for growth factors that can be released by the secreted proteases and thereby further aid tumor growth and progression. Other survival advantages of tumor cells include: the ability to utilize multiple modes of motility, thrive in acidic microenvironments, and the tumor cell’s ability to hijack stromal and immune cells to foster their own migration and survival. In order to reduce metastasis, we must focus our efforts on addressing the survival advantages that tumor cells have acquired.

Keywords

Proteolysis Tumor cell motility Modeling breast cancer Tumor microenvironment 3D cell culture Extracellular matrix Live-cell imaging Breast cancer 

Notes

Acknowledgments

We thank M. Sameni, C. Jedeszko and P. Lynch for the contribution of figures. We would like to thank laboratory members for their discussions and contributions to the development of 3D/4D cultures and co-cultures. This work was supported in part by R01 CA131990 (RRM and BFS) and R21 CA175931 (BFS) from the National Institutes of Health and Congressionally Directed Medical Research ProgramW81XWH-12-1-0024(KOO) from the Department of Defense. Imaging was performed in the Microscopy, Imaging and Cytometry Resources Core, which is supported, in part, by NIH Center grant P30 CA022453 to the Karmanos Cancer Institute at Wayne State University, and the Perinatology Research Branch of the National Institutes of Child Health and Development at Wayne State University.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Kingsley O. Osuala
    • 1
  • Kyungmin Ji
    • 1
  • Raymond R. Mattingly
    • 1
  • Bonnie F. Sloane
    • 1
  1. 1.Department of Pharmacology and Barbara Ann Karmanos Cancer InstituteWayne State University School of MedicineDetroitUSA

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