Exposed collagenous proteins in tumor extracellular matrix (dn-collagen)

Exposed collagenous proteins in the tumor extracellular matrix (ECM) represent a distinct structural state of collagen characterized by denatured, fragmented, or proteolytically remodeled fibers. In healthy tissues, collagen typically exists in a stable triple-helical conformation; however, the high metabolic activity and elevated levels of matrix metalloproteinases (MMPs) in tumors lead to the unfolding of these helices, revealing "cryptic" epitopes that are otherwise hidden (Xu et al., 2001). These exposed sites serve as unique biochemical markers for malignancy and are actively involved in promoting tumor cell adhesion, migration, and angiogenesis (Caron et al., 2016). Therapeutic strategies targeting these proteins often utilize specialized peptides, such as Collagen Hybridizing Peptides (CHPs), or monoclonal antibodies like HUIV26 that specifically recognize the unfolded state of collagen (Li et al., 2017). By binding to these sites, drugs can be selectively delivered to the tumor microenvironment, or the interaction between tumor cells and the remodeled ECM can be disrupted to inhibit metastasis (Frontiers in Oncology, 2023). This targeting approach offers high specificity for the tumor stroma while minimizing impact on healthy, quiescent tissues where collagen remains in its native helical form.

Other names

Denatured collagenCryptic collagen epitopesRemodeled tumor collagenUnfolded collagenProteolyzed collagenDamaged collagen

Selective binding to denatured or proteolytically remodeled collagen strands via triple-helix hybridization or cryptic epitope recognition to deliver therapeutic payloads or disrupt pro-tumorigenic signaling.