Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Small Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells induce Oxygen-dependent Cell Invasion

Bianca Cruz Pachane
,
Ana Carolina Caetano Nunes
ORCID logo ,
Thais Regiani Cataldi
,
Kelli Cristina Micocci
,
Bianca Caruso Moreira
,
Carlos Alberto Labate
,
Heloisa Sobreiro Selistre-de-Araujo
,
Wanessa Fernanda Altei
* ORCID logo
Version 1 : Received: 24 August 2022 / Approved: 26 August 2022 / Online: 26 August 2022 (14:08:23 CEST)

A peer-reviewed article of this Preprint also exists.

Pachane, B.C.; Nunes, A.C.C.; Cataldi, T.R.; Micocci, K.C.; Moreira, B.C.; Labate, C.A.; Selistre-de-Araujo, H.S.; Altei, W.F. Small Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells Induce Oxygen-Dependent Cell Invasion. Int. J. Mol. Sci. 2022, 23, 12646. Pachane, B.C.; Nunes, A.C.C.; Cataldi, T.R.; Micocci, K.C.; Moreira, B.C.; Labate, C.A.; Selistre-de-Araujo, H.S.; Altei, W.F. Small Extracellular Vesicles from Hypoxic Triple-Negative Breast Cancer Cells Induce Oxygen-Dependent Cell Invasion. Int. J. Mol. Sci. 2022, 23, 12646.

Abstract

Hypoxia, a condition of low oxygenation frequently found in triple-negative breast tumors (TNBC), promotes extracellular vesicle (EV) secretion and favors cell invasion, a complex process in which cell morphology is altered, dynamic focal adhesion spots are created, and ECM is re-modeled. Here, we investigated the invasive properties triggered by TNBC-derived hypoxic small EV (SEVh) in vitro in cells cultured under hypoxic and normoxic conditions, using pheno-typical and proteomic approaches. SEVh characterization demonstrated increased protein abundance and diversity over normoxic SEV (SEVn), with enrichment in pro-invasive pathways. In normoxic cells, SEVh promotes invasive behavior through pro-migratory morphology, in-vadopodia development, ECM degradation and matrix metalloprotease (MMP) secretion. Pro-teome profiling of normoxic cells exposed to SEVh determined enrichment in metabolic processes and cell cycle, modulating cell health to escape apoptotic pathways. In hypoxia, SEVh was re-sponsible for proteolytic and catabolic pathway inducement, interfering with integrin availabil-ity and gelatinase expression. Overall, our results demonstrate the importance of hypoxic signal-ing via SEV in tumors for the early establishment of metastasis.

Keywords

Hypoxia; Extracellular vesicles; Breast Cancer; Cell Invasion

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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