The localization of a cell type-specific, soluble fibroblast surface antigen (SFA) was studied by immunofluorescence and by scanning electron microscopy of the same cells. The antigen had an uneven distribution forming streaks on chick embryo fibroblasts. It was localized to membrane processes and ridges, with a diameter of 50–200 nm. The processes extended from the periphery of the cells to the substratum or to other cells. Trypsin treatment completely removed detectable amounts of SFA. The antigen was detectable within 1 h after trypsin-treated cells were reseeded. The reappearance of SFA correlated with the restoration of membrane processes.

Fibroblasts transformed by Rous sarcoma virus (RSV) showed loss of all or most SFA. When normal cells were transformed without subcultivation and trypsinization a fibrillar extracellular network of SFA remained under the transformed fibroblasts while the cells themselves were negative in immunofluorescence. When fibroblasts infected by RSV mutants were transferred to nonpermissive temperature for transformation new SFA was detected within 2 h. These data lead us to propose that loss of stabilizing and anchoring effect of SFA molecules in fibrillar cell surface structures may be critical in altered growth control and malignant transformation.