Remodeling the Microenvironment before Occurrence and Metastasis of Cancer

Abstract

Tumorigenesis and progression of cancer are complex processes which transformed cells and stromal cells interact and co-evolve. Intrinsic and extrinsic factors cause the mutations of cells. The survival of transformed cells critically depends on the circumstances which they reside. The malignant transformed cancer cells reprogram the microenvironment locally and systemically. The formation of premetastatic niche in the secondary organs facilitates cancer cells survival in the distant organs. This review outlines the current understanding of the key roles of premalignant niche and premetastatic niche in cancer progression. We proposed that a niche facilitates survival of transformed cells is characteristics of senescence, stromal fibrosis and obese microenvironment. We also proposed the formation of premetastatic niche in secondary organs is critically influenced by primary cancer cells. Therefore, it suggested that strategies to target the niche can be promising approach to eradicate cancer cells.

Keywords: co-evolution; premalignant niche; premetastatic niche.

Figure 1

Schematic diagram of formation of the premalignant niche and premetastatic niche. Mutations result either from DNA replication errors or from the damaging events. Accumulation of unrepaired mutations transforms normal cells. The survival of transformed cells critically depends on the circumstances which they reside. The niche at high risk of malignant transformation is associated with aging, fibrosis and obesity. Bone marrow-derived cells (BMDC) including haematopoietic progenitors, mesenchymal stem cells, endothelial progenitor cells comprise the main component in the premetastatic niche. Tumor-derived secreted factors (TDSFs) are crucial in creating a supportive microenvironment at the metastatic site. Chemokines or cytokines derived from the primary cancer cells reprogramming the distant organs and contribute to the establishment of premetastatic niche. Exosomes participate in cell-to-cell communication by the molecules enriched in their membrane, remodeling the microenvironment of target organs and help the formation of premetastatic niche.