Cancer cells transfer invasive properties through microRNAs contained in collagen tracks

Abstract

Invasion is a prerequisite for metastasis formation. During tumor development, type I collagen overexpression increases tumor microenvironment stiffness, facilitating cancer cell dissemination. During breast cancer cell migration in 2D and 3D matrices, we observed membrane debris left behind, attached to the collagen fibrils, along the migration path. We named these structures collagen -tracks. Their formation is stimulated by the interaction between the extracellular matrix (ECM) and matrix receptors, such as discoidin domain receptor 1 (DDR1). They present a specific nucleic acid and protein contents. When deposited by highly invasive breast cancer cells, internalized collagen tracks reprogram non-invasive cells into highly pro-metastatic ones, increasing their ECM degradation and invasive capacities. This cell reprogramming is dependent on specific microRNAs (miRNAs) identified in the collagen tracks. Collagen tracks thus represent a form of cell-cell communication important for driving tumor invasion that could be targeted to prevent metastasis.

Keywords: CP: Cancer; ECM degradation; cell-cell communication; collagen; collagen fibrils; discoidin domain receptor 1; microRNA; migration; triple negative breast cancer; tumor invasion.