Recombinant humanized collagen type III with high antitumor activity inhibits breast cancer cells autophagy, proliferation, and migration through DDR1

Int J Biol Macromol. 2023 Jul 15:243:125130. doi: 10.1016/j.ijbiomac.2023.125130. Epub 2023 May 30.

Abstract

Breast cancer (BC) has become the most common cancer in the world and lacks safe and efficient treatment. The novel biomaterial recombinant humanized collagen type III (rhCOLIII) has been reported to have various biological functions, such as promoting skin extracellular matrix regeneration and improving the cell microenvironment, but its role in breast cancer is unclear. In this study, we first found that rhCOLIII inhibited the proliferation, migration, and invasion of breast cancer cells (BCCs) but had no effect on the survival of normal breast epithelial cells. In addition, rhCOLIII not only promoted apoptosis and dormancy of BCCs but also inhibited autophagy within BCCs. Subsequently, RNA-Seq analysis suggested that DDR1 may be a key target for rhCOLIII to exert antitumor effects, and we validated that inhibition of DDR1 eliminated the effects of rhCOLIII on the proliferation, migration, apoptosis, dormancy and autophagy of BCCs. Moreover, rhCOLIII treatment was found to reduce the tumorigenic activity of BCCs in animal experiments and to upregulate DDR1 protein expression while inhibiting autophagy at the tissue level. Therefore, rhCOLIII may serve as a potential treatment method for BC patients and is expected to improve the prognosis of patients.

Keywords: Autophagy; Breast cancer; DRR1; Recombinant humanized collagen type III.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Collagen Type III* / pharmacology
  • Neoplasms*

Substances

  • Collagen Type III