Adult, foetal and transformed fibroblasts display different migratory phenotypes on collagen gels: evidence for an isoformic transition during foetal development.

Data are presented indicating that the migration of fibroblasts into three-dimensional collagen gels is affected by cell density. We have defined a 'cell density migration index' (CDMI) to express this behavioural response in quantitative terms. The results of a survey of 77 different cell types indicate that the CDMI values expressed by normal adult skin fibroblasts and transformed cell lines fall into two distinct, non-overlapping groups. Measurement of the CDMI therefore provides an additional means of distinguishing between normal and transformed cells and may be used in conjunction with other commonly recognized criteria (e.g. anchorage-independent growth) to assess expression of a transformed phenotype in vitro. It is of interest to note that the CDMI values expressed by foetal cells define a group lying intermediate between normal and transformed cells. Both uncloned and cloned foetal cells have been observed to undergo a stable transition to expression of CDMI values characteristic of adult cells when followed throughout the duration of their in vitro lifespan. In addition to providing a novel means of distinguishing between normal adult and foetal cells, our results suggest that foetal fibroblasts undergo an 'isoformic' transition at some point in their developmental history, which is manifest in vitro by the expression of an adult CDMI.