Trastuzumab modulates the protein cargo of extracellular vesicles released by erbb2+ breast cancer cells

Silvia Marconi, Sara Santamaria, Martina Bartolucci, Sara Stigliani, Cinzia Aiello, Maria Cristina Gagliani, Grazia Bellese, Andrea Petretto, Katia Cortese, Patrizio Castagnola

Research output: Contribution to journalArticlepeer-review

Abstract

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, im-munoblot, and high‐resolution mass spectrometry analyses on EVs purified by differential centrif-ugation 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 glycosyl-ated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, in-cluding TOP1. Because these proteins are functionally associated with organelle organization, cyto-kinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs.

Original languageEnglish
Article number199
JournalMembranes
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2021

Keywords

  • Breast cancer
  • CD63
  • Extracellular vesicles
  • HER2
  • Immuno-electron microscopy
  • Mitochondria
  • Proteomic analysis
  • TOP1
  • Trastuzumab

ASJC Scopus subject areas

  • Chemical Engineering (miscellaneous)
  • Process Chemistry and Technology
  • Filtration and Separation

Fingerprint Dive into the research topics of 'Trastuzumab modulates the protein cargo of extracellular vesicles released by erbb2<sup>+</sup> breast cancer cells'. Together they form a unique fingerprint.

Cite this