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Researchers developed novel nanobodies (Nb3 and Nb4) that specifically detect Tenascin-C (TNC), a molecule promoting tumor growth. These nanobodies restore cell adhesion and block TNC

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Area of Science:

  • Biochemistry
  • Immunology
  • Oncology

Background:

  • Tenascin-C (TNC) is an extracellular matrix molecule known to promote tumor progression.
  • Current methods for detecting TNC in clinical tissue samples are limited.
  • TNC plays a role in immune suppression within the tumor microenvironment.

Purpose of the Study:

  • To generate and characterize novel single-domain nanobodies specific for human TNC (hTNC).
  • To evaluate the potential of these nanobodies for detecting hTNC in human tissues.
  • To assess the functional impact of these nanobodies on TNC-mediated effects, including cell adhesion and immune cell tethering.

Main Methods:

  • Generation of dromedary single-domain nanobodies (Nb3 and Nb4).
  • Biochemical characterization using ELISA, western blot, and isothermal fluorescence titration.
  • Microscopic analysis including negative electron microscopy, immunofluorescence, and immunohistochemistry.
  • Functional assays assessing cell adhesion and dendritic cell immobilization.

Main Results:

  • Nb3 and Nb4 were highly specific for hTNC, binding to distinct sequences within fibronectin type III repeats.
  • Both nanobodies successfully detected hTNC in various human tissues, including tumors and ulcerative colitis samples.
  • Nb3 and Nb4 restored tumor and mesangial cell adhesion to fibronectin/TNC substrata.
  • The nanobodies blocked TNC-mediated tethering of dendritic cells.

Conclusions:

  • Novel hTNC-specific nanobodies (Nb3 and Nb4) have been developed.
  • These nanobodies are valuable tools for detecting TNC in clinical settings.
  • The nanobodies can inhibit TNC's pro-tumorigenic functions, including immune suppression and impaired cell adhesion, offering therapeutic potential.