1. Academic Validation
  2. Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer

  • Br J Cancer. 2018 May;118(11):1442-1452. doi: 10.1038/s41416-018-0078-x.
Rashmi Bharti 1 Goutam Dey 1 Anjan Kumar Das 2 Mahitosh Mandal 3
Affiliations

Affiliations

  • 1 School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India.
  • 2 Department of Pathology, Calcutta National Medical Collage, Kolkata, West Bengal, 70014, India.
  • 3 School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India. mahitosh@smst.iitkgp.ernet.in.
Abstract

Background: Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis.

Methods: We employed various in-vitro and in-vivo techniques and clinical samples.

Results: We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast Cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic Cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast Cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen.

Conclusions: Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast Cancer environment.

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