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.

Scientific Reports
|May 6, 2026
PubMed

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.

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