Short communication: neurofibromatosis fibroblasts: slow growth and abnormal morphology

We hypothesized that skin fibroblasts from patients with neurofibromatosis (NF) may have abnormalities of growth in tissue culture to correlate with the clinical abnormalities of overgrowth and malignancy seen in this disease. Using five lines of NF cells, age- and passage-matched to normal controls, we found that NF fibroblasts grew more slowly and stopped growing at a lower population density than normal cells (P less than 0.0005). The same cells also incorporated [3H]thymidine at a lower rate than normal skin fibroblasts (9,330 +/- 3,240 versus 42,100 +/- 6,840; P less than 0.01). The addition of epidermal growth factor to the medium stimulated the growth of both the normal and the NF fibroblasts; however, the stimulation of the NF fibroblasts was inadequate to fully correct the slow growth rate (P less than 0.025). NF cells (N = 5) were found to be morphologically different from normal skin fibroblasts (N = 5) in culture by light microscopy. NF cells were larger (approximately 9 X 10(4) X 2 X 10(4) versus 2 X 10(4) X 2 X 10(4) A), pleomorphic, and failed to form confluent monolayers when growth ceased. Speculation These data indicate that there may be an underlying abnormality of growth regulation in neurofibromatosis. The slow growth of neurofibromatosis fibroblasts, and their diminished response to epidermal growth factor, provides a means for studying the growth abnormality of neurofibromatosis in tissue culture. In addition, the expression of this abnormality may serve as a marker for the disease.