Tangled fibroblasts in tumor‐stroma interactions

Fibrogenesis, expressed as "desmoplasia," is found in many kinds of tumors and considered to be associated with malignancy. In fact, fibroblasts in cancer stroma have attracted considerable attention in the last 2 decades. Although it is accepted that fibroblasts are important in tumor development and progression, the mechanisms involved are highly complex and difficult to disentangle. Which role do fibroblasts play in tumors-are they friends or foes? Can fibroblasts account for the relationship between inflammation, fibrosis and tumor? Do fibroblasts acquire gene changes during carcinogenesis and how many signaling pathways are involved in tumor-stroma interactions? What is the outcome of fibroblast activation in tumors-senescence, death or recovery to a progenitor cell such as the fibrocyte? These questions still need further exploration and will be discussed in this review.