Extracellular matrix heterogeneity regulates three-dimensional morphologies of breast adenocarcinoma cell invasion

Cancer cell invasion is a fundamental aspect of metastasis and a major cause of mortality in patients[1]. The invasive potential of cancer cells is largely dependent on their ability to degrade and migrate through extracellular matrix (ECM) barriers. During invasion, cancer cells form asymmetrical morphology to escape from their original location and invade into surrounding microenvironment. Various migration types can be broadly categorized into single-cell migration, multicellular streaming and collective migration, regulated by physical and molecular determinants of the cells and from stromal tissues[2]. Well-defined in vitro experiments have allowed precise delineation of the various cell migration mechanisms involving receptor-ligand interactions, but their complexity and synergistic effects of physical and molecular guiding principles make it still challenging to apparently identify the mechanisms[2, 3]. Furthermore, tumour cells have plasticity adaptively changing structure of ECM, invasion mode, and interaction with other cells by various extra- and intra-cellular mechanisms[2, 3]. Previous in vitro studies have failed revealing the complexity and plasticity, because they have regarded invaded tissue as a homogeneous and passive scaffold[2]. In the present study, we have considered the invaded tissue as heterogeneous ECM, a regulator of tumor cell behavior simultaneously allowing cancer cells to lead either proteolytic or non-proteolytic invasion[4].