Researchers from the Institut Curie, Paris, suggest that carcinoma-associated fibroblasts (CAF) and cancer cells may cooperate in the process of cancer invasion. Their work, based on colon cancer cells, will be presented at the ASCB/IFCB meeting in Philadelphia.
“In situ” means “in place”; however, it certain occasions, a carcinoma cell does not want to keep its primary place.
The basement membrane is a very thin sheet of fibers that usually cradles the cells standing above it. This membrane stands between a cancer cell in situ, the surrounding tissue of the fibroblasts and the extracellular matrix; it is also the barrier that keeps primary tumors from scattering to the matrix below. The first cancer-associated movement is to perforate the basement membrane to try to invade the remaining tissues; the question though, remains: how do cancer cells manage to do this?
Fibroblasts are usually found in the connective tissue that produces extracellular matrix and in other structural animal proteins like collagen. Carcinoma-associated fibroblasts (CAF), for instance, are matrix proteinases that could be used for breaking this membrane.
Currently, it is not known if cancer cells invade and break the basement membrane barrier or if fibroblasts actually help their invasion.
Alexandros Glentis and his research colleagues wanted to determine whether cancer cells or CAFs were responsible for breaking the basement membrane. As such, they used human colon cancer cells and primary human fibroblasts that were isolated from tumors and adjacent tissues. Researchers compared CAF cells from colon tumors to normal fibroblasts (NAFs), both isolated from the same patients. The results showed that both CAFs and NAFs induced invasion and migration of a noninvasive colon cancer cell line.
Additionally, researchers compared a standard basement membrane with fibroblasts embedded in collagen, observing that only CAFs could stimulate invasion of cancer cells. Through proteomic evaluations, the team confirmed that CAFs produced more extracellular matrix proteins, proteases and proteins that can modify the membrane (in comparison with NAFs).
The cancer-CAF cooperation shows that cancer cells already communicate with fibroblasts before they move to the basement membrane. Ongoing studies are being developed to further investigate this phenomenon.