Related Experiment Video
Updated: May 8, 2026

Analysis of Cell Migration within a Three-dimensional Collagen Matrix
Published on: October 5, 2014
Targeting the D93 cryptic collagen epitope alters integrin α2β1-dependent cellular migration and collagen remodeling
Jordan N Miner1,2,3, Christopher L Emmerling4, Joshua D Hamilton1,2,3
1Department of Chemical and Biomedical Engineering, University of Maine, Orono, ME, USA.
Abstract:
Targeting the tumor-associated extracellular matrix (ECM) offers a promising strategy for breast cancer therapy. During cancer progression, collagen remodeling within the ECM exposes cryptic collagen epitope sites that antibodies can selectively recognize. Here, we investigate the therapeutic potential of targeting the D93 cryptic collagen epitope in 3D human metastatic breast cancer spheroids derived from MDA-MB-231 and MCF10CA1a (M4) cell lines embedded in collagen type I hydrogels. Treatment with monoclonal antibody (mAb) D93 reduced cellular migration into collagen type I hydrogels, an effect likely mediated by integrin α2β1. Two-photon microscopy further revealed that breast cancer cells drive the exposure of D93 sites and alter collagen architecture at both the fiber and fibril levels. Interestingly, collagen remodeling was altered more in the MDA-MB-231 spheroid models whereas the reduction in cellular migration was more pronounced in the M4 spheroid models, indicating a cell-line specific response to mAb D93. Together, these findings suggest that mAb D93 may inhibit integrin α2β1-dependent metastatic migration in breast cancer.
Insights
Targeting cryptic collagen epitopes with monoclonal antibody D93 can inhibit breast cancer cell migration. This antibody shows potential for treating metastatic breast cancer by targeting the tumor extracellular matrix.
Area of Science:
- Oncology
- Biochemistry
- Biomaterials
Background:
- The tumor microenvironment, particularly the extracellular matrix (ECM), is a key player in breast cancer progression.
- Collagen remodeling during cancer progression exposes cryptic epitopes, offering potential therapeutic targets.
- Monoclonal antibodies (mAbs) can selectively target these exposed epitopes for cancer therapy.
Purpose of the Study:
- To investigate the therapeutic potential of targeting the D93 cryptic collagen epitope in 3D breast cancer models.
- To evaluate the effect of mAb D93 on cellular migration and collagen architecture in metastatic breast cancer spheroids.
Main Methods:
- Utilized 3D human metastatic breast cancer spheroids (MDA-MB-231 and MCF10CA1a/M4) embedded in collagen type I hydrogels.
- Administered monoclonal antibody (mAb) D93.
- Employed two-photon microscopy to visualize collagen remodeling and cellular migration.
- Assessed cell-line specific responses to mAb D93.
Main Results:
- mAb D93 treatment reduced cellular migration into collagen type I hydrogels, potentially via integrin α2β1.
- Breast cancer cells were observed to drive the exposure of D93 sites and alter collagen at fiber and fibril levels.
- Collagen remodeling differences were noted between MDA-MB-231 and M4 spheroid models.
- Cellular migration inhibition varied between cell lines, indicating a cell-specific response to mAb D93.
Conclusions:
- mAb D93 demonstrates potential in inhibiting breast cancer cell migration within the tumor microenvironment.
- Targeting the D93 cryptic collagen epitope may represent a novel therapeutic strategy for metastatic breast cancer.
- The efficacy of mAb D93 may be dependent on cancer cell line and associated collagen remodeling patterns.
Related Concept Videos
Intracellular Signaling Affects Focal Adhesions
Some...
The Tumor Microenvironment
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.

