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Aggressive serous epithelial ovarian cancer is potentially propagated by EpCAM+CD45+ phenotype

Oncogene volume 37, pages 2089–2103 (2018)Cite this article

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Abstract

Epithelial ovarian carcinoma (EOC) patients often acquire resistance against common chemotherapeutic drugs like paclitaxel and cisplatin. The mechanism responsible for the same is ambiguous. We have identified a putative drug-resistant tumour cell phenotype (EpCAM+CD45+) in the ascitic fluid of EOC patients, which appears to originate from the primary tumour. These cells represent the major tumour burden and are more drug resistant compared to EpCAM+ tumour cells due to the over-expression of SIRT1, ABCA1 and BCL2 genes. We have found that the entire EpCAM+CD45+ population is highly invasive with signature mesenchymal gene expression and also consists of subpopulations of ovarian cancer stem cells (CD133+ and CD117+CD44+). Additionally, we demonstrate that the EpCAM+CD45+ tumour cells over-express major histocompatibility complex class I antigen, which enable them to evade the natural killer cell-mediated immune surveillance. Preliminary evidence obtained in OVCAR-5 cells suggests that exosomes, secreted by non-tumour cells of the ascitic fluid, play an important role in rendering drug resistance and invasive properties to the cancer cells. Identification of such aggressive tumour cells and deciphering their origin is important for designing better drug targets for EOC.

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Acknowledgements

AM is grateful for the generous support provided by the Department of Biotechnology, Government of India to the Centre of Molecular Medicine, NII. We would like to thank Mr. Nila Ram and Mr. Ajay Sharma for acquiring confocal images. AM would like to thank Dr. Ayub Qadri, Scientist (NII, New Delhi), Prof. NK Mehra (AIIMS, New Delhi) and Dr. Awadhesh Pandit (NCBS, Bangalore) for valuable discussion in some parts of the study. Also, we are thankful to Dr. TR Santhosh Kumar (RGCB, Thiruvananthapuram, Kerala) for providing the OVCAR-5 cell line.

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Author notes

  1. Md Zahid Akhter

    Present address: Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

  2. Surender K Sharawat

    Present address: Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

  3. Veena Kochat

    Present address: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

  4. Mallika Ramakrishnan

    Present address: Georg Speyer Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany

  5. Umesh Kumar

    Present address: Genomics Facility, Department of Biochemistry, University of Delhi South Campus, New Delhi, India

  6. Md Zahid Akhter, Surender K Sharawat and Vikash Kumar contributed equally to this work.

Authors and Affiliations

  1. Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India

    Md Zahid Akhter, Surender K Sharawat, Vikash Kumar, Veena Kochat, Zaffar Equbal, Mallika Ramakrishnan, Umesh Kumar, Sandeep Mathur, Lalit Kumar & Asok Mukhopadhyay

  2. Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

    Sandeep Mathur

  3. Department of Medical Oncology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

    Lalit Kumar

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Akhter, M.Z., Sharawat, S.K., Kumar, V. et al. Aggressive serous epithelial ovarian cancer is potentially propagated by EpCAM+CD45+ phenotype. Oncogene 37, 2089–2103 (2018). https://doi.org/10.1038/s41388-017-0106-y

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