Letter: Comments on reported observations of cells spreading on the upper surfaces of other cells in culture

Although we state that "the inability of the upper cell surface to support spreading may be a general phenomenon ," we point out in the text (reference 4, p. 219) that "we limit our conclusions only to the cell types used in this study and only to in vitro conditions." In fact, we cite one case where this may not apply. In his letter, Dr. Prop cites several cases where cells in culture are apparently spreading on the upper surfaces of other cells. Elsdale and Bard (5) report that epithelial cells "adhere to and spread out upon fibroblastic lawns." Visser et al. 06) state that primary mouse mammary fibroblastic cells move actively on a mouse mammary epithelial sheet. We have examained these papers with care and are not entirely convinced that spreading on the upper surfaces of cells in vitro actually occurred in the cases cited. Our reservations concerning the spreading of epithelial cells on a "lawn" of fibroblasts (5) are the following. (a) A spreading epithelial sheet adheres to a plastic sub-stratum predominantly at the margin of the sheet, and it is the marginal cells that play the major role in epithelial spreading (3, 14). Since the area of adhesion to the substratum is relatively small compared to the area of the entire spreading cell sheet (3), it is conceivable that marginal cells send loeomotory processes (lamellipodia) to the plastic or collagenous substratum through the gaps which occur frequently in a fibroblast sheet. (b) The possibility that the fibroblasts have secreted a collagen carpet or that the epithelial cells and fibroblasts have produced a "basement membrane" between them has not been explored (8). (c) Translocation of a given cell over the upper surface of another cell is in no instance shown in any detail. This is inferred by the authors from films in which, unfortunately, the magnification is too low and the cultures too dense to tell whether cells spread by lamellipodia adhering to the plastic substratum or to the upper cell surface. In order to observe in detail the contact behavior of cells on top of a sheet, they must be observed as individuals and followed continuously, as we did (4). In passing, we also question the general conclusion of Elsdale and Bard (5) that the inability of epithelial sheets to support cell spreading in culture fits them for their in vivo role at free surfaces in epithelial-mesenchymal …