Quantitative Proteomics for the Identification of Differentially Expressed Proteins in the Extracellular Vesicles of Cervical Cancer Cells

Viruses. 2023 Mar 8;15(3):702. doi: 10.3390/v15030702.

Abstract

The extracellular vesicles (EVs) in a tumoral microenvironment can exert different functions by transferring their content, which has been poorly described in cervical cancer. Here, we tried to clarify the proteomic content of these EVs, comparing those derived from cancerous HPV (+) keratinocytes (HeLa) versus those derived from normal HPV (-) keratinocytes (HaCaT). We performed a quantitative proteomic analysis, using LC-MS/MS, of the EVs from HeLa and HaCaT cell lines. The up- and downregulated proteins in the EVs from the HeLa cell line were established, along with the cellular component, molecular function, biological processes, and signaling pathways in which they participate. The biological processes with the highest number of upregulated proteins are cell adhesion, proteolysis, lipid metabolic process, and immune system processes. Interestingly, three of the top five signaling pathways with more up- and downregulated proteins are part of the immune response. Due to their content, we can infer that EVs can have a significant role in migration, invasion, metastasis, and the activation or suppression of immune system cells in cancer.

Keywords: HPV; HeLa cells; cancer; exosomes; extracellular vesicles; proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Liquid
  • Extracellular Vesicles* / metabolism
  • Female
  • HeLa Cells
  • Humans
  • Papillomavirus Infections* / metabolism
  • Proteins / metabolism
  • Proteomics
  • Tandem Mass Spectrometry
  • Tumor Microenvironment
  • Uterine Cervical Neoplasms* / metabolism

Substances

  • Proteins

Grants and funding

This research was funded by CONACYT, through the Fondo Sectorial de Investigación para la Educación, grant number A1-S-33418, and Facultad de Medicina y Cirugía, UABJO.