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Breast cancer metastasis: Putative therapeutic role of vascular cell adhesion molecule-1

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Abstract

Background

Breast cancer is a notable cause of cancer-related death in women worldwide. Metastasis to distant organs is responsible for ~90% of this death. Breast cells convert to malignant cancer cells after acquiring the capacity of invasion/intravasation into surrounding tissues and, finally, extravasation/metastasis to distant organs (i.e., lymph nodes, lungs, bone, brain). Metastasis to distant organs depends on interactions between disseminated tumor cells (DTCs) and the endothelium of blood vessels present in the tumor microenvironment. Among several known endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) has been found to be involved in this process. It has been shown that VCAM-1 is aberrantly expressed in breast cancer cells and that it can bind to its natural ligand α4β1integrin, also denoted as very late antigen 4 (VLA-4). This binding appears to be responsible for the metastasis of breast cancer cells to lung, bone and brain. The α4β1 integrin - VCAM-1 interaction thus represents a potential therapeutic target for metastatic breast cancer cells. The development of inhibitors of this interaction may be instrumental for the clinical management of breast cancer patients.

Conclusions

This study focuses on recent progress on the role of VCAM-1, an important glycoprotein belonging to the immunoglobulin (Ig) superfamily of cell surface adhesion molecules in breast cancer angiogenesis, survival and metastasis. Targeting VCAM-1, expressed on the surface of breast cancer cells, and/or its specific ligand VLA-4/α4β1 integrin, expressed on cells at the site of metastasis, may be a useful strategy to reduce breast cancer cell invasion and metastasis. Various approaches to therapeutically target VCAM-1 and VLA-4 are also discussed.

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Acknowledgements

T.P. Khaket was supported by the Korea Research Fellowship Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (KRF Grant No.2016H1D3A1938249).

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Authors and Affiliations

  1. Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, India

    Rohit Sharma, Chanchala Dutta, Bornisha Chakraborty & Tapan Kumar Mukherjee

  2. Department of Botany, University of Jammu, Jammu, India

    Rohini Sharma

  3. Department of Biotechnology, Daegu University, Gyeongsan, Gyeongbuk, Republic of Korea

    Tejinder Pal Khaket

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  1. Rohit Sharma
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Sharma, R., Sharma, R., Khaket, T.P. et al. Breast cancer metastasis: Putative therapeutic role of vascular cell adhesion molecule-1. Cell Oncol. 40, 199–208 (2017). https://doi.org/10.1007/s13402-017-0324-x

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