Glycan signatures for the identification of cisplatin-resistant testicular cancer cell lines: Specific glycoprofiling of human chorionic gonadotropin (hCG)

Cancer Med. 2022 Feb;11(4):968-982. doi: 10.1002/cam4.4515. Epub 2022 Jan 19.

Abstract

Background: Testicular cancer (TC) is the most frequent type of cancer among young men aged between 15 and 34 years. TC is treated using cisplatin, but 3%-5% of TC patients fail to respond to cisplatin, with a very bad to fatal prognosis. Accordingly, it is most important to quickly and readily identify those TC patients who are resistant to cisplatin treatment.

Methods: This study seeks to investigate changes in the glycosylation associated with cisplatin resistance to TC cell lines.

Results: A specific glycoprofiling of human chorionic gonadotropin (hCG) was analysed in three TC cell lines and one cell line of female origin. A typical calibration curve for hCG glycoprofiling showed a dynamic range up to 50 ng/ml, with a limit of detection of 0.3 ng/ml and assay reproducibility represented by relative standard deviation of 3.0%. Changes in the glycan signatures on hCG were analysed in cisplatin-sensitive cell lines and in their cisplatin-resistant sub-lines using an enzyme-linked lectin assay (ELLA) protocol. An immobilised antibody was applied to a selective capture of hCG from a cytoplasmic fraction of cell lysates with final incubation using a lectin from a panel of 17 lectins.

Conclusion: The results suggest that one particular lectin Dolichos biflorus agglutinin (DBA) can selectively discriminate sensitive TC cell lines from resistant TC cell lines. Moreover, there are additional lectins which can provide useful information about the strength of cisplatin resistance.

Keywords: cell lines; germ cell tumour; glycans; glycosylation; human chorionic gonadotropin; lectins; testicular cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Line
  • Chorionic Gonadotropin / metabolism
  • Cisplatin* / pharmacology
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lectins
  • Male
  • Neoplasms, Germ Cell and Embryonal
  • Polysaccharides / pharmacology
  • Reproducibility of Results
  • Testicular Neoplasms* / drug therapy
  • Testicular Neoplasms* / metabolism
  • Young Adult

Substances

  • Chorionic Gonadotropin
  • Lectins
  • Polysaccharides
  • Cisplatin

Supplementary concepts

  • Testicular Germ Cell Tumor