Stromal cells in tumor microenvironment
Stromal cells in tumor microenvironment Tumor microenvironment (TME) plays a crucial role in cancer progression, metastasis, and response to therapy. Among the various cellular components of TME, stromal cells are particularly significant due to their dynamic interactions with tumor cells. These stromal cells include fibroblasts, immune cells, endothelial cells, and mesenchymal stem cells, all of which contribute to creating a supportive niche that facilitates tumor growth and survival.
Stromal cells in tumor microenvironment Cancer-associated fibroblasts (CAFs) are one of the most prominent stromal cell types within the TME. Derived from normal fibroblasts or mesenchymal stem cells, CAFs are reprogrammed by tumor cells to adopt an activated phenotype characterized by increased secretion of growth factors, cytokines, and extracellular matrix components. These secretions promote tumor cell proliferation, invasion, and angiogenesis. Moreover, CAFs modulate the immune response by secreting immunosuppressive factors, thus enabling the tumor to evade immune surveillance.
Endothelial cells form the lining of new blood vessels through a process called angiogenesis, which is essential for tumor growth beyond a certain size. Tumors release angiogenic factors like vascular endothelial growth factor (VEGF), stimulating endothelial cells to form new vasculature that supplies oxygen and nutrients. The abnormal vasculature also facilitates metastatic dissemination by providing pathways for tumor cells to enter circulation. Stromal cells in tumor microenvironment
The immune component of stromal cells in the TME includes macrophages, lymphocytes, and myeloid-derived suppressor cells. Tumor-associated macrophages (TAMs) often acquire a pro-tumoral phenotype, secreting factors that promote tissue remodeling, angiogenesis, and suppression of anti-tumor immune responses. Similarly, regulatory T cells and myeloid cells contribute to creating an immunosuppressive environment that hinders the body’s natural ability to combat tumor cells. Stromal cells in tumor microenvironment
Stromal cells in tumor microenvironment Mesenchymal stem cells (MSCs), which can migrate to tumors, also participate in the TME by differentiating into various stromal lineages and secreting factors that support tumor growth. They may promote resistance to chemotherapy and radiation therapy by inducing survival pathways in tumor cells.
The interactions between tumor cells and stromal cells are bidirectional, with tumor cells shaping the behavior of stromal components and vice versa. This crosstalk involves a complex network of cytokines, chemokines, and growth factors, creating a supportive niche that not only sustains tumor growth but also contributes to therapy resistance. Consequently, targeting stromal components has become an attractive strategy in cancer therapy. Approaches such as inhibiting CAF activation, normalizing tumor vasculature, and modulating immune cells are currently under investigation to disrupt this supportive microenvironment.
Stromal cells in tumor microenvironment Understanding the multifaceted roles of stromal cells in the tumor microenvironment enhances our ability to develop more effective therapies. By targeting both tumor cells and their supportive stromal counterparts, there is potential to improve treatment outcomes and reduce the likelihood of relapse, ultimately advancing the fight against cancer.
