Tumor microenvironment remodeling by cancer cell-released tracks on type I collagen

ABSTRACT: Metastasis is the leading cause of cancer-related deaths. During this process, tumor cells acquire invasive and migratory capacities in order to invade the surrounding tissues. To achieve this, the tumor microenvironment is altered to facilitate cancer cells proliferation and dissemination. Multiple mechanisms are involved in metastasis formation, including cell-cell communications through the tumor microenvironment and extracellular matrix remodeling. Extracellular vesicles (EVs) such as exosomes or migrasomes are already known to induce pro-tumor features such as migration, promoting tumor development and metastasis formation. Here we describe a new type of extracellular vesicles (referred as tracks) released by cancer cells and specifically attached along collagen fibers during the cell migration. We characterized these tracks, their formation, their ultrastructure as well as their molecular composition in terms of proteins and nucleic acids (miRNA), showing that they are different from classical extracellular vesicles known so far. These tracks are promoted and identified by discoidin domain receptor 1 (DDR1) in the extracellular space. Moreover, these tracks are very stable structures and surrounding cells can internalize them. After internalization, they modify the differentiation status and the phenotype of recipient cells, promoting epithelial to mesenchymal transition, cell proliferation, matrix degradation and also invasion. These data show that these collagen-associated EVs (tracks) have a role in cell-cell communication and participate in the tumor microenvironment remodeling. Consequently, these cancer-related tracks could be a new player in the tumor invasion process.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Dupuy Jean-William  

LAB HEAD: Frederic Saltel

PROVIDER: PXD035152 | Pride | 2026-02-24

REPOSITORIES: Pride