4.7 Article

Upstream Hedgehog signaling components are exported in exosomes of cervical cancer cell lines

Journal

NANOMEDICINE
Volume 13, Issue 17, Pages 2127-2138

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2018-0143

Keywords

cervical cancer; exosome cargo; exosome characterization; exosome DNA; exosomes; export; Hedgehog signaling; paracrine signaling; patched; silver staining

Funding

  1. ExoCan Healthcare Technologies Pvt Ltd
  2. Department of Science and Technology, Government of India [DST-PURSE Phase II/RC/2016/944]
  3. Department of Biotechnology, Government of India [6242-P34/RGCB/PMD/ALCB/2015]
  4. ICMR (Indian Council of Medical Research) [5/13/38/2014 NCDIII E Office 73143]
  5. DST SERB-EMR Grant [EM/2017/004018]
  6. ICMR Fellowship [2017-2834/CMB-BMS]

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Aim: To investigate export of Hedgehog pathway (Hh) proteins Patched1, Smoothened, Sonic hedgehog and Indian hedgehog in cervical cancer cell line (CaCx) exosomes. Methods: Exosomes were isolated and characterized by Western blotting, scanning electron microscopy and in a colorimetric assay. Nucleic acids (RNA, DNA) and protein content of exosomes were analyzed. Hh pathway proteins in exosomes were detected using Western blotting. Results: CaCx secrete bio-macromolecule (DNA, RNA and proteins) enriched exosomes. CaCx exosomes contained higher amount of RNA with respect to DNA. CaCx preferentially exported Hh proteins (Patched1, Smoothened, Sonic hedgehog, Indian hedgehog) in their exosomes. Cellular uptake assay revealed rapid internalization of CaCx exosomes in human umbilical vein endothelial cells. Conclusion: Our study showed that Hh proteins are exported in CaCx exosomes.

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