Role of stroma in Cancer and wound healing

Stroma is describes as a connective tissue containing type I collagen and fibroblasts. However, it is closely associated with other extra cellular matrix (ECM) components that play a central role in wound healing and in cancer. The stromal cellular components such as activated fibroblasts interact with complex protein networks that include growth factors, structural protein or proteinases in order to initiate and sustain an extensive remodelling process. However, this process is unregulated in cancer and leads to uncontrolled cell proliferation and invasion within tissues, metastasis and therapeutic resistance. The early stages of tumor development, the basement membrane surrounding the tumor cells are destroyed by proteinases secreted from cancer or stromal cells. This allows the tumor cells to contact the stroma. The aberrant interactions between the cancer cells and its microenvironment significantly alter the composition of the stroma and contribute to the development of human cancers, including breast. The major difference between wound healing and cancer is that wound healing is a self-limiting process. However, the edges of a tumor are constantly expanding; this difference is related to differences in the components of the microenvironment or stroma. Activated stroma is associated with more ECM-producing fibroblasts. In tissue homeostasis, natural fibroblasts are silent and inactive within the ECM and interact with their surroundings through cellular receptors. Fibroblasts are activated in wound healing, however, as soon as the wound is fully healed; most of these active fibroblasts are destroyed by apoptosis. Cancer is considered a wound that never heals, because apoptosis-activated fibroblasts are not destroyed and play an important role in tumorigenesis. In tumors, activated fibroblasts are referred to as Cancer-associated fibroblasts (CAFs). CAFs differ from normal fibroblasts in increasing ECM production and collagen protein. They are also an important source of ECM-degrading proteases that play an important role in tumorigenesis. In normal cells, the components of stroma preserve tissue microenvironment and restrict cell growth spatially and temporally. However, in tumor stroma, fibroblast activity can promote tumor progression and prevent response to treatment.

کلیدواژه ها:

Wound healing ، Cancer ، Stroma ، Fibroblast