Exosome secretome and mediated signaling in breast cancer patients with nontuberculous mycobacterial disease

Julie V Philley,Barbara A Brown-Elliott,Richard J Wallace,Jeana L Benwill,Anbarasu Kannan,Santanu Dasgupta,Hernaina Bains,Foram Thakkar,Megan S Devine,Sudeep Gupta,David E Griffith,Ammar Alqaid,Varsha Taskar,James G Fox

doi:10.18632/oncotarget.14964

Julie V Philley, Barbara A Brown-Elliott + Show 12 more

Open Access

https://doi.org/10.18632/oncotarget.14964

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Abstract

Bronchiectasis Nontuberculous mycobacterium (NTMnb) infection is an emerging health problem in breast cancer (BCa) patients. We measured sera exosome proteome in BCa-NTMnb subjects and controls by Mass Spectroscopy. Extracellular matrix protein 1 (ECM1) was detected exclusively in the circulating exosomes of 82% of the BCa-NTMnb cases. Co-culture of ECM1+ exosomes with normal human mammary epithelial cells induced epithelial to mesenchymal transition accompanied by increased Vimentin/CDH1 expression ratio and Glutamate production. Co-culture of the ECM1+ exosomes with normal human T cells modulated their cytokine production. The ECM1+ exosomes were markedly higher in sera obtained from BCa-NTMnb subjects. Exclusive expression of APN, APOC4 and AZGP1 was evident in the circulating exosomes of these BCa-NTMnb cases, which predicts disease prevalence independent of the body max index in concert with ECM1. Monitoring ECM1, APN, APOC4 and AZGP1 in the circulating exosomes could be beneficial for risk assessment, monitoring and surveillance of BCa-NTMnb.

Highlights

Nontuberculous mycobacterial lung disease (NTM) is a growing health problem in North America and worldwide [1]
Among the 118 unique proteins, extracellular matrix protein 1 (ECM1) expression was detected in 82% (14/17) of the breast cancer (BCa)-NTMnb subjects (Figure 2A, Table 1)
A number of unique spectra and 4 peptides (Figure 2A) of Extracellular matrix protein 1 (ECM1) were detected in the circulating exosomes of the 14 BCa-NTMnb subjects

Summary

Introduction

Nontuberculous mycobacterial lung disease (NTM) is a growing health problem in North America and worldwide [1]. NTM lung disease occurs inindividuals with anatomic lung abnormalities, certain genetic disorders, such as cystic fibrosis, and individuals with no known immunologic abnormalities [2]. The frequency of NTM patients with disease characterized radiographically by nodules and bronchiectasis or nodular bronchiectatic disease (NTMnb) in particular, has increased over the past few decades [1]. The majority of these cases involved Mycobacterium avium complex (MAC) infection and occurs primarily in Caucasian women with a specific body habitus [3,4]. There is an increasing rate of NTMnb disease in Caucasian women with a current diagnosis or history of breast cancer. There are no molecular factors known to be associated with the development of NTMnb disease in these BCa patients

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