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Stromal cells in tumor microenvironment and breast cancer

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Abstract

Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic _targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion, and metastasis. In breast cancer, CAFs not only promote tumor progression but also induce therapeutic resistance. Accordingly, _targeting CAFs provides a novel way to control tumors with therapeutic resistance. This review summarizes the current understandings of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. In addition, the effects of other stromal components such as endothelial cells, macrophages, and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to categorize patients into a specific and confirmed subtype for personalized treatment.

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Acknowledgments

We apologize to the many authors whose excellent work we could not cite owing to space limitation. Research in the authors’ laboratory is supported by National Natural funding of China (81272404, 81071747, 81202087, 81172520), National Key Program (973) for Basic Research of China (2011CB510106, 2011CB504300), Shanghai Education Committee Key Discipline and Specialties Foundation (J50208), the Program for Professor of Special Appointment (Eastern Scholar to J. Wang) at Shanghai Institutions of Higher Learning, and Shanghai Pujiang Program (10PJ1406400), Shanghai Committee of Science and Technology (11DZ2260200), and the Program of Shanghai Municipal Health Bureau Subject Chief Scientist (XBR20110052), National Institutes of Health grant P01 CA093900. This research was supported in part by the grants from Leading Academic Discipline Project of Shanghai Municipal Education Commission (Grant Number: J50208); National Natural Science Foundation of China (Grant Number: 81202087; 81172520).

Conflict of interest statement

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Shanghai Ruijin Hospital, Comprehensive Breast Health Center, Shanghai, 200025, China

    Yan Mao, David H. Garfield & Kunwei Shen

  2. Department of Urology, University of Michigan, Ann Arbor, MI, 48109, USA

    Evan T. Keller

  3. University of Colorado Comprehensive Cancer Center, Aurora, CO, 80045, USA

    David H. Garfield

  4. Department of Biochemistry and Molecular & Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Jianhua Wang

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  1. Yan Mao
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  2. Evan T. Keller
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  3. David H. Garfield
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  4. Kunwei Shen
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  5. Jianhua Wang
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Correspondence to Kunwei Shen or Jianhua Wang.

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Mao, Y., Keller, E.T., Garfield, D.H. et al. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev 32, 303–315 (2013). https://doi.org/10.1007/s10555-012-9415-3

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