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Perspectives on the role of brain cellular players in cancer-associated brain metastasis: translational approach to understand molecular mechanism of tumor progression

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Abstract

Brain metastasis is one of the leading causes of death among cancer patients. Cancer cells migrate to various sites and harbor different niche in the body which help cancer cells in their survival. The brain is one of the safest place where cancer cells are protected from immune cells. Breast, lung, and melanoma cancer cells have high propensity to migrate towards the brain. To enter the brain, cancer cells have to cross the blood brain barrier. Survival and finding new niche in the brain are directed by several mechanisms in which different cellular players take part such as astrocytes, microglia, Schwann cells, satellite cells, oligodendrocytes, and ependymal cells. Usually, cancer cells highjack the machinery of brain cellular players to survive in the brain environment. It has been shown that co-culture of M2 macrophage with cancer cells leads to increased proliferation and survival of cancer cells. One of the challenges of understanding brain metastasis is appropriate model system to understand dynamic interaction of cancer cells and brain cellular players. To meet this challenge, microfluidic-based devices are employed which can mimic the dynamic conditions as well as can be used for culturing human cells for personalized therapy. In this review, we have systematically reviewed the current status of the role of cellular players in brain metastasis along with explaining how translational approach of microfluidics can be employed for finding new drug target as well as biomarker for brain metastasis. Finally, we have also commented on the mechanism of action of drugs against brain metastasis.

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Funding

Seema Sehrawat is the recipient of BioCARe award from the Department of Biotechnology, Govt. of India. Shiv Nadar Foundation is acknowledged for providing the PhD fellowship to Mr. Masoom Raza, Mr. Naveen Kumar, and Mr. Peeyush Prasad. Aaron Goldman is supported by the Breast Cancer Alliance Young Investigator Award.

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Author notes

  1. Masoom Raza and Peeyush Prasad contributed equally to this work.

Authors and Affiliations

  1. Brain Metastasis and NeuroVascular Disease Modeling Lab, Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, NCR, India

    Masoom Raza, Peeyush Prasad, Pragya Gupta, Naveen Kumar, Taruna Sharma & Seema Sehrawat

  2. Department of Pediatrics, Division of Pediatric Neurology, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA

    Mandeep Rana

  3. Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA

    Aaron Goldman & Seema Sehrawat

  4. Mitra Biotech, Integrative Immuno-Oncology Center, Woburn, MA, 01801, USA

    Aaron Goldman

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  1. Masoom Raza
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  2. Peeyush Prasad
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  3. Pragya Gupta
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  4. Naveen Kumar
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  7. Aaron Goldman
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  8. Seema Sehrawat
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Correspondence to Aaron Goldman or Seema Sehrawat.

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AG is an employee of the Mitra Biotech and holds equity. All other authors declare no conflict of interest.

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Raza, M., Prasad, P., Gupta, P. et al. Perspectives on the role of brain cellular players in cancer-associated brain metastasis: translational approach to understand molecular mechanism of tumor progression. Cancer Metastasis Rev 37, 791–804 (2018). https://doi.org/10.1007/s10555-018-9766-5

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