Bisecting GlcNAc modification diminishes the pro‐metastatic functions of small extracellular vesicles from breast cancer cells

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.

Download Full-text

Extracellular vesicles produced in B cells deliver tumor suppressor miR-335 to breast cancer cells disrupting oncogenic programming in vitro and in vivo

Scientific Reports ◽

10.1038/s41598-018-35968-2 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 6

Author(s):

Gonzalo Almanza ◽

Jeffrey J. Rodvold ◽

Brian Tsui ◽

Kristen Jepsen ◽

Hannah Carter ◽

...

Keyword(s):

Breast Cancer ◽

B Cells ◽

Tumor Suppressor ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Breast Cancer Cells

Download Full-text

Extracellular vesicles from triple-negative breast cancer cells promote proliferation and drug resistance in non-tumorigenic breast cells

Breast Cancer Research and Treatment ◽

10.1007/s10549-018-4925-5 ◽

2018 ◽

Vol 172 (3) ◽

pp. 713-723 ◽

Cited By ~ 17

Author(s):

Patricia Midori Murobushi Ozawa ◽

Faris Alkhilaiwi ◽

Iglenir João Cavalli ◽

Danielle Malheiros ◽

Enilze Maria de Souza Fonseca Ribeiro ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Breast Cells

Download Full-text

Abstract LB-116: Neuromedin U drives increased expression of TGFβ1 in HER2-positive breast cancer cells and their extracellular vesicles: a novel biomarker of response to HER-targeted drugs

10.1158/1538-7445.am2016-lb-116 ◽

2016 ◽

Author(s):

Vanesa G. Martinez ◽

Lorraine O’Driscoll

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Breast Cancer Cells ◽

Targeted Drugs ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Download Full-text

Linking integrins and EVs in metastasis

Science Signaling ◽

10.1126/scisignal.abe3353 ◽

2020 ◽

Vol 13 (649) ◽

pp. eabe3353

Author(s):

Leslie K. Ferrarelli

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Extracellular Vesicles ◽

Breast Cancer Cells

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

Download Full-text

Mesenchymal stem cell-derived extracellular vesicles may promote breast cancer cell dormancy

Journal of Tissue Engineering ◽

10.1177/2041731418810093 ◽

2018 ◽

Vol 9 ◽

pp. 204173141881009 ◽

Cited By ~ 4

Author(s):

Jake Casson ◽

Owen G Davies ◽

Carol-Anne Smith ◽

Matthew J Dalby ◽

Catherine C Berry

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Cell Proliferation ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cancer Cells ◽

Cancer Cell ◽

Extracellular Vesicles ◽

Breast Cancer Cells ◽

Cell Dormancy

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.

Download Full-text