Progress in mass spectrometry-based proteomic research of tumor hypoxia

Abstract

A hypoxic microenvironment effects various signaling pathways in the human body, including those that are critical for normal physiology and those that support tumorigenesis or cancer progression. A hypoxic tumor microenvironment, in particular, modulates cell migration, invasion and resistance to radiotherapy and chemotherapy. Development of the mass spectrometry (MS) technique has allowed for expansion of proteomic study to a wide variety of fields, with the study of tumor hypoxia being among the latest to enjoy its benefits. In such studies, changes in the proteome of tumor tissue or cells induced by the hypoxic conditions are analyzed. A multitude of hypoxic regulatory proteins have already been identified, increasing our understanding of the mechanisms underlying tumor occurrence and development and representing candidate reference markers for tumor diagnosis and therapy. The present review provides the first summary of the collective studies on tumor microenvironment hypoxia that have been completed using MS-based proteomic techniques, providing a systematic discussion of the benefits and current challenges of the various applications.

Application of Advanced Mass Spectrometry-Based Proteomics to Study Hypoxia Driven Cancer Progression

“…In such studies, differential proteomes across various types of cells/tissue/clinical samples in association of hypoxic conditions are analyzed. Proteins that are repeatedly identified across different samples suggest their likelihood of having an active role in hypoxia regulation and thus may lead to the generation of novel targeted cancer therapies (Table 1) (76,77). On the other hand, a protein (or a set of proteins) of high confidence that is (are) exclusively identified in specific samples could act as candidate biomarkers for clinical use (78)(79)(80)(81).…”

Quantitative Proteomics Reveals the Beneficial Effects of Low Glucose on Neuronal Cell Survival in an in vitro Ischemic Penumbral Model

“…Several studies focusing on the cellular proteomic changes based on either hypoxia alone or OGD treatment in neuronal cells provided some valuable information to understand how OGD influences cellular changes and contributes to the neuronal damage and death (Jin et al, 2004 ; Datta et al, 2009 ; Zhou et al, 2011 ; Herrmann et al, 2013 ). However, only limited proteins were identified and most of the OGD models were based on tumor-derived neuronal cells (Jin et al, 2004 ; Datta et al, 2009 ; Zhou et al, 2011 ; Herrmann et al, 2013 ; Djidja et al, 2014 ; Qi et al, 2014 ; Gao et al, 2017 ). To mimic ischemic penumbra, using neuronal cells of non-tumor origin for quantitative proteomic analysis might allow us better to identify the ischemic stress-induced pathways for developing therapeutic interventions.…”