Targeting the D93 cryptic collagen epitope alters integrin α2β1-dependent cellular migration and collagen remodeling

Research Square
|February 6, 2026
PubMed

Insights

Targeting cryptic collagen epitopes with monoclonal antibody D93 can reduce breast cancer cell migration. This antibody may inhibit integrin α2β1-dependent metastasis by remodeling the tumor extracellular matrix.

Area of Science:

  • Oncology
  • Biochemistry
  • Cell Biology

Background:

  • The tumor microenvironment, particularly the extracellular matrix (ECM), is a critical factor in breast cancer progression.
  • Collagen remodeling during cancer progression exposes cryptic epitopes, offering potential therapeutic targets.
  • Integrin α2β1 plays a role in cell adhesion and migration within the ECM.

Purpose of the Study:

  • To investigate the therapeutic potential of targeting the D93 cryptic collagen epitope in 3D breast cancer models.
  • To assess the effect of monoclonal antibody (mAb) D93 on cellular migration and collagen architecture.
  • To determine cell-line specific responses to mAb D93 treatment.

Main Methods:

  • Utilized 3D human metastatic breast cancer spheroids (MDA-MB-231 and MCF10CA1a/M4) embedded in collagen type I hydrogels.
  • Administered mAb D93 to spheroid cultures.
  • Employed two-photon microscopy to visualize collagen architecture and D93 epitope exposure.
  • Quantified cellular migration into the collagen matrix.

Main Results:

  • mAb D93 treatment reduced cellular migration into collagen type I hydrogels.
  • Breast cancer cells were observed to drive D93 epitope exposure and alter collagen fiber and fibril architecture.
  • Collagen remodeling differences were noted between MDA-MB-231 and M4 spheroid models.
  • Reduced cellular migration was more pronounced in M4 spheroid models, suggesting cell-line specificity.

Conclusions:

  • mAb D93 demonstrates potential in inhibiting breast cancer cell migration within the ECM.
  • The antibody's mechanism may involve targeting integrin α2β1-dependent pathways.
  • Findings highlight the cell-specific efficacy of targeting cryptic collagen epitopes in breast cancer therapy.

Related Concept Videos

Fibril-associated Collagen01:11

Fibril-associated Collagen

Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
3.4K
Collagens are the Major Structural Proteins of ECM01:13

Collagens are the Major Structural Proteins of ECM

Three main types of fibers are secreted by fibroblasts: collagen fibers, elastic fibers, and reticular fibers. Collagen fiber is made from fibrous protein subunits linked together to form a long, straight fiber. Collagen fibers, while flexible, have great tensile strength, resist stretching, and give ligaments and tendons their characteristic resilience and strength. These fibers hold connective tissues together, even during the body's movement.
Connective tissue proper includes loose...
5.8K
Type IV Collagen of Basal Lamina01:05

Type IV Collagen of Basal Lamina

Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen  forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
A type IV collagen molecule has six alpha chains which can...
3.1K
Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
11.2K
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
5.5K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.3K