Involvement of Actin Filaments in the Cytotoxic Effect of GD2-Specific Antibodies

I I Doronin1,2, I V Kholodenko3, A A Zubareva1

  • 1M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

Insights

GD2-specific antibodies combat neuroblastoma by inducing cell death. This study reveals that actin microfilaments are crucial for this antibody-mediated tumor cell death, highlighting a new therapeutic target.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • GD2-specific antibodies are utilized in high-risk neuroblastoma therapy.
  • The precise mechanisms of antibody-triggered cytotoxic signaling in tumor cells are not fully understood.

Purpose of the Study:

  • To investigate the role of cellular components in the cytotoxic effects of GD2-specific antibodies.
  • To elucidate the signaling pathways involved in antibody-dependent cell death of neuroblastoma.

Main Methods:

  • Utilized inhibitor analysis to study the involvement of actin microfilaments.
  • Tested the effect of cytochalasin D on GD2+ tumor cell lines treated with GD2-specific antibodies.

Main Results:

  • Actin microfilaments were identified as key players in antibody-induced cell death.
  • Cytochalasin D significantly antagonized the cytotoxic effect, increasing cell survival by over 20%.
  • A notable decrease in DNA fragmentation was observed in treated cells.

Conclusions:

  • Actin cytoskeleton dynamics are essential for the efficacy of GD2-specific antibody therapy.
  • Targeting actin microfilaments could enhance the antitumor effects of GD2-based immunotherapies for neuroblastoma.

Related Concept Videos

Actin Filament Depolymerization01:19

Actin Filament Depolymerization

Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
3.9K
Formation of Higher-order Actin Filaments01:11

Formation of Higher-order Actin Filaments

The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin...
3.6K
Generation of Straight or Branched Actin Filaments01:14

Generation of Straight or Branched Actin Filaments

The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
3.8K
Actin Treadmilling01:18

Actin Treadmilling

Actin filaments undergo polymerization and depolymerization from either end. The polymerization and depolymerization rates depend on the cytosolic concentration of free G-actins. The polymerization rate is generally higher at the plus or barbed end, while the depolymerization rate is higher at the minus or pointed end. At a steady state, critical concentration describes the concentration of free G-actin monomers at which the polymerization rate at the plus end is equal to that of the...
9.7K
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.5K
Introduction to Actin01:26

Introduction to Actin

Actin is a highly conserved cytoskeletal protein found abundantly in eukaryotic cells. It constitutes 10% weight of the total cellular protein in muscle cells, while in non-muscle cells, it is lower and makes up around 1–5 percent of the total cell protein. Actin found in the unicellular amoebae and complex multicellular animals is around 80% similar, demonstrating their conservation over a billion years of evolution.  Actin coding genes are conserved within species and across...
6.6K