scholarly journals Trastuzumab Modulates the Protein Cargo of Extracellular Vesicles Released by ERBB2+ Breast Cancer Cells

Author(s):  
Silvia Marconi ◽  
Sara Santamaria ◽  
Martina Bertolucci ◽  
Sara Stigliani ◽  
Cinzia Aiello ◽  
...  

Cancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is a ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance, and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Tz induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. As these proteins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 199
Author(s):  
Silvia Marconi ◽  
Sara Santamaria ◽  
Martina Bartolucci ◽  
Sara Stigliani ◽  
Cinzia Aiello ◽  
...  

Cancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is an ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles (EVs) released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here, we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Trastuzumab (Tz) induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. Because these proteins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.


2021 ◽  
Vol 153 ◽  
pp. 106519
Author(s):  
Alejandra Garcia-Hernandez ◽  
Elizabeth Leal-Orta ◽  
Javier Ramirez-Ricardo ◽  
Pedro Cortes-Reynosa ◽  
Rocio Thompson-Bonilla ◽  
...  

2018 ◽  
Vol 172 (3) ◽  
pp. 713-723 ◽  
Author(s):  
Patricia Midori Murobushi Ozawa ◽  
Faris Alkhilaiwi ◽  
Iglenir João Cavalli ◽  
Danielle Malheiros ◽  
Enilze Maria de Souza Fonseca Ribeiro ◽  
...  

2015 ◽  
Vol 35 (2) ◽  
pp. 1147-1152 ◽  
Author(s):  
HYE YOUNG CHOI ◽  
NAMMI PARK ◽  
JAE BOEM NA ◽  
EUN SOOK KO ◽  
JAE-YONG PARK ◽  
...  

2020 ◽  
Vol 13 (649) ◽  
pp. eabe3353
Author(s):  
Leslie K. Ferrarelli

Integrins mediate the uptake of extracellular vesicles into breast cancer cells.


Biology Open ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. bio038323 ◽  
Author(s):  
Carolina D'Alesio ◽  
Grazia Bellese ◽  
Maria Cristina Gagliani ◽  
Anastasia Lechiara ◽  
Martina Dameri ◽  
...  

2018 ◽  
Vol 9 ◽  
pp. 204173141881009 ◽  
Author(s):  
Jake Casson ◽  
Owen G Davies ◽  
Carol-Anne Smith ◽  
Matthew J Dalby ◽  
Catherine C Berry

Disseminated breast cancer cells have the capacity to metastasise to the bone marrow and reside in a dormant state within the mesenchymal stem cell niche. Research has focussed on paracrine signalling factors, such as soluble proteins, within the microenvironment. However, it is now clear extracellular vesicles secreted by resident mesenchymal stem cells into this microenvironment also play a key role in the initiation of dormancy. Dormancy encourages reduced cell proliferation and migration, while upregulating cell adhesion, thus retaining the cancer cells within the bone marrow microenvironment. Here, MCF7 breast cancer cells were treated with mesenchymal stem cell–derived extracellular vesicles, resulting in reduced migration in two-dimensional and three-dimensional culture, with reduced cell proliferation and enhanced adhesion, collectively supporting cancer cell dormancy.


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