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

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.

Human Platelets Contain, Translate, and Secrete Azurocidin; A Novel Effect on Hemostasis.

Platelets play a significant role in hemostasis and perform essential immune functions, evidenced by the extensive repertoire of antimicrobial molecules. Currently, there is no clear description of the presence of azurocidin in human platelets. Azurocidin is a 37 kDa cationic protein abundant in neutrophils, with microbicidal, opsonizing, and vascular permeability-inducing activity. Therefore, this work aimed to characterize the content, secretion, translation, and functions of azurocidin in platelets. Our results show the presence of azurocidin mRNA and protein in α-granules of platelet and megakaryoblasts, and stimulation with thrombin, ADP, and LPS leads to the secretion of free azurocidin as well as within extracellular vesicles. In addition, platelets can translate azurocidin in a basal or thrombin-induced manner. Finally, we found that the addition of low concentrations of azurocidin prevents platelet aggregation and activation. In conclusion, we demonstrate that platelets contain, secrete, and translate azurocidin, and this protein may have important implications for hemostasis.

Extracellular Vesicles in Cervical Cancer and HPV Infection.

Since their description, extracellular vesicles (EVs) have shown growing relevance in cancer progression. These cell structures contain and transfer molecules such as nucleic acids (including DNA and RNA), proteins, and lipids. Despite the rising information about EVs' relationship with cancer, there is still scarce evidence about their content and function in cervical cancer. Interestingly, the composition and purposes of some cellular molecules and the expression of oncogenic proteins packaged in EVs seem modified in HPV-infected cells; and, although only the E6 oncogenic protein has been detected in exosomes from HPV-positive cells, both E6/E7 oncogenes mRNA has been identified in EVs; however, their role still needs to be clarified. Given that EVs internalizing into adjacent or distant cells could modify their cellular behavior or promote cancer-associated events like apoptosis, proliferation, migration, or angiogenesis in receptor cells, their comprehensive study will reveal EV-associated mechanisms in cervical cancer. This review summarizes the current knowledge in composition and functions of cervical cancer and HPV Infection-derived EVs.