4.6 Article

Adhesion of LHRH/EphA2 to human Triple Negative Breast Cancer tissues

Publisher

ELSEVIER
DOI: 10.1016/j.jmbbm.2022.105461

Keywords

Adhesion forces/energies; Human triple negative breast cancer tissue; LHRH/EphA2-receptors; Atomic force microscopy; Detection and treatment of cancer

Funding

  1. World Bank African Centers of Excellence [AUST/PAMI/2015 5415-NG]
  2. WPI Global Fellowship Program
  3. WPI Innovation Fellowship Program
  4. African Development Bank (ADB)

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This paper presents a combined experimental and theoretical study on the adhesion between molecular recognition units and receptors on tumor surfaces. The results show that the adhesion forces and energies between high-grade TNBC tissues and Luteinizing Hormone Releasing Hormone (LHRH) or Epherin type A2 (EphA2) are significantly higher than those with normal human breast tissues. These findings have important implications for the development of targeted nanostructures for the detection and treatment of TNBC.
The adhesive interactions between molecular recognition units (such as specific peptides and antibodies) and antigens or other receptors on the surfaces of tumors are of great value in the design of targeted nanoparticles and drugs for the detection and treatment of specific cancers. In this paper, we present the results of a combined experimental and theoretical study of the adhesion between Luteinizing Hormone Releasing Hormone (LHRH)/ Epherin type A2 (EphA2)-AFM coated tips and LHRH/EphA2 receptors that are overexpressed on the surfaces of human Triple Negative Breast Cancer (TNBC) tissues of different histological grades. Following a histochemical and immuno-histological study of human tissue extracts, the receptor overexpression, and their distributions are characterized using Immunohistochemistry (IHC), Immunofluorescence (IF), and a combination of fluorescence microscopy and confocal microscopy. The adhesion forces between LHRH or EphA2 and human TNBC breast tissues are measured using force microscopy techniques that account for the potential effects of capillary forces due to the presence of water vapor. The corresponding adhesion energies are also determined using adhesion theory. The pull off forces and adhesion energies associated with higher grades of TNBC are shown to be greater than those associated with normal/non-tumorigenic human breast tissues, which were studied as controls. The observed increase in adhesion forces and adhesion energies are also correlated with the increasing incidence of LHRH/EphA2 receptors at higher grades of TNBC. The implications of the results are discussed for the development of targeted nanostructures for the detection and treatment of TNBC.

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