Fibroblasts from cancer patients display a mixture of both foetal and adult-like phenotypic characteristics

Abstract

We have previously reported that foetal and adult fibroblasts display distinctive migratory phenotypes when cultured on three-dimensional collagen gels. Both skin and tumour-derived fibroblasts from a significant proportion of patients with breast cancer were subsequently observed to display foetal-like migratory behaviour. In the accompanying paper concerned with the biochemical basis of these observations, we presented evidence that foetal fibroblasts and the foetal-like fibroblasts of cancer patients produce a soluble migration-stimulating factor (MSF) not made by normal adult cells. Data are presented here indicating that: (1) the spontaneous foetal-to-adult transition in migratory phenotype that foetal fibroblasts undergo after approximately 50-55 population doublings in vitro is correlated with a cessation of MSF production; (2) breast cancer patient fibroblasts do not undergo such a phenotypic transition and continue to produce MSF for their entire in vitro lifespan. These foetal-like cancer patient fibroblasts do, however, resemble normal adult cells by a number of other criteria, including population doubling potential, enhanced migration in the presence of serum compared to platelet-poor plasma, saturation cell density and morphology in confluent culture. These data indicate that the fibroblasts of breast cancer patients express a mixture of both foetal and adult phenotypic characteristics. Such a finding is consistent with published information indicating that foetal-to-adult transitions in various fibroblast phenotypic characteristics occur in a temporally disparate fashion during normal development, and further imply that cancer patient fibroblasts have undergone only certain of these transitions.