Question

Describe the role of cancer associated fibroblasts in the development of cancer. By keeping in mind that cancers are named as wounds that do not heal.

Answer 1

The stroma of a wound and a tumor are alike with similarities such as fibroblast activation, increased extracellular matrix (ECM) protein production and intensive remodeling processes. And thus tumor is often reffered as wounds that do not heal as the cancer cells distort the normal wound healing program and migrate from the initiation site to invade the adjacent cells.

CAF ( cancer associated fibroblasts) are fibroblasts found in the stroma of human cancers but differ from normal fibroblasts in their increased collagen and ECM protein production and up-regulated secretion of pro-tumor factors. These fibroblasts share similarities with the myofibroblasts which are involved in wound healing. Their role is given as follows:

1. It is the cancer associated fibroblasts that contribute to tumor proliferation, invasion, and metastasis by secreting various growth factors, cytokines, chemokines, and degradation of extracellular matrix (ECM) proteins of the normal cells.

2. The tumor stroma provide microenvironment for tumor growth and consists of fibroblasts (CAF), ECM, vascular endothelial cells, and immune cells which act as a barrier in promoting tumorigenesis and drug delivery.

3. They are also involved in the ECM remodeling as tumor cells expresse the members of matrix metalloproteinase family (MMPs)which selectively degrade the type IV collagen and laminin (constitutents of the basement membrane) and thus contribute to tumor proliferation.

4. Cancer associated fibroblasts secrete IL- 6 which is an angiogenic cytokine and stimulates the production of pro-angiogenic factors, such as fibroblast growth factor 2 (FGF2) and VEGF. Therefore CAF regulate angiogenesis in the stroma providing essential nutrients for highly proliferative tumor cells.

5. Provide assistance to tumor cells in overcoming immune surveillance by recruiting immunosuppressive cells like M2 macrophages and myeloid-derived suppressor cells (MDSC).