Tumor Microenvironment: Molecular Mechanisms and Signaling Pathways Involved in Metastatic Progression

Despite important advances in cancer treatments, metastasis remains the major cause of cancer mortality. In the complex tumor microenvironment, several malignant and non-malignant cell types, as well as components of the extracellular matrix (ECM), interact together in promoting the metastatic process. Stromal cells already present in the tumor microenvironment (TME) or recruited from distant sites are “educated” by cancer cells through a dynamic cross-talk involving growth factors, cytokines, chemokines, miRNAs. These primed cells, including cancer-associated fibroblasts, tumor-associated macrophages, and tumor-associated mesenchymal stem cells, acquire a pro-metastatic function that supports tumor cells in each step of the metastatic cascade. Importantly, the bi-directional communication between tumor microenvironment and cancer cells induces the epithelial-mesenchymal-transition (EMT) that in turn elicits profound morphological and functional changes in tumor cells triggering a mesenchymal-like phenotype with higher invasive potential. A crucial step in the establishment of metastases includes the formation of a pre-metastatic niche where recruited stromal cells contribute to creating a favorable microenvironment permitting cancer cell seeding. To successfully germ in a distant site, cancer cells need to find nutrients, an ECM that can support their attachment and stromal cells that help them with paracrine signaling to survive and proliferate in the new environment.

The aim of this Research Topic is to review recent data regarding the underlying mechanisms and signaling pathways involved in this complex communication between all the players involved in metastatic progression.

In this Research Topic we welcome Original Research, Reviews and Mini-Reviews articles focusing on but not limited too:

1) Recruitment of stromal cells in the tumor microenvironment
2) Stromal and tumor cell-derived soluble factors (growth factors, cytokines, chemokines, miRNAs)
3) Role of EMT program in cancer cell dissemination
4) Phenotypic switching of stromal cells educated by cancer cells
5) Signal pathways involved in the cross-talk between cancer cells and tumor microenvironment
6) ECM remodeling
7) Contribution of the microenvironment in each step of the metastatic cascade
8) Role of stromal cells in pre-metastatic niche establishment