The role of cancer associated fibroblasts (CAFs) in seed and soil theory

The metastatic homing of cells is described as the metastatic implantation of the cells that is not a chance (seed), on the contrary, influenced by the interaction between metastatic cancer cells and the penetration of organ specific microorganisms. Several types of tumors, especially those that originate from the ovary and the digestive tract, are known to have a strong tendency to peritoneal cavity metastasis. Intraperitoneal malignancy is caused by a cross-contamination between invasive cancer cells and peritoneum-retaining cells. Intraperitoneal malignancy development is caused by interactions between invasive cancer cells (seed) and peritoneal normal cells (soil). Cancer cells, endothelial, epithelial, smooth muscle cells, and quiescent fibroblasts stimulate paracrine signaling mechanisms, implying to the seed and soil theory. Studies have shown that cancer-associated fibroblasts (CAFs), which are the main constituent of the supportive tissue (stroma), play an important role in tumor progression, metastasis, and therapeutic resistance. CAFs have been shown to be able to produce various types of cytokines, including interleukin (IL)-6, CXCL-8, IL-8, growth factors (FGF, HGF, TGF-β, VEGF), extracellular matrix proteins, remodeling enzymes, tenascin-C, periostin, fibronectin, and matrix metalloproteinase (MMP)-1, and thus support all stages of tumor progression. Studies have shown that CAFs play a role in carcinogenesis due to transforming growth factor (TGF)-β signaling. The role of TGF-β in the formation of a tumor is due to the suppression of the immune system. Interestingly, both senescent and non-senescent CAFs have shown a variety of activities, including more aggressive cancer phenotypes. It has also been shown that IL-32 released from cancer-dependent fibroblasts increased breast cancer invasion and metastases through the integrin β3-P38 MAPK signaling. According to the findings, it can be concluded that if the activity of the fibroblasts in the cancerous environments is controlled, it can be hoped that the rate of growth, proliferation and invasion of the cancerous cells can be controlled.