Fetal-like fibroblasts: their production of migration-stimulating factor and role in tumor progression.

Abstract

Cancer pathogenesis is a multistep process involving the occurrence of an initiating genetic lesion and a series of subsequent events collectively referred to as progression [,]. In spite of the general acceptance of this model, little information is currently available regarding either the frequency at which initiating genetic lesions occur or the proportion of initiated cells that proceed on to develop into a clinically recognizable malignancy. Our assessment of the literature suggests that initiating events may be a relatively common occurrence and that only a small proportion of these cells actually go on to produce clinical tumors. Seen in this context, the various events that contribute to tumor progression play a critical role in determining the kinetics of disease development and may thereby furnish a potential target for intervention in individuals believed to be at elevated risk. Recent studies have indicated that the gradual acquisition during tumor progression of more ‘aggressive’ phenotypic characteristics, such as diminished growth control [], local invasion [], and metastasis [], also involve the accumulation of genetic lesions within the emerging population of (pre-) neoplastic cells. The primary role of genetic lesions in the process of cancer development is further suggested by the occurrence of well-defined hereditary syndromes characterized by increased susceptibility to specific types of cancer (e.g., carcinoma of the breast) []. The identification and mapping of the relevant genes is currently being pursued with great vigor [].