Figure 1.

Collagen type XI inhibits cancer-associated fibroblast (CAF) functions. (A) CAFs bind to collagen type XI. CAFs were seeded on monomeric (mono) or fibrillar (fib) collagen type I and collagen type XI for 40 min. Cells were stained with crystal violet and absorbance was read at 595 nm. Bovine serum albumin (BSA) and fibronectin were used as negative and positive control for cell adhesion, respectively, (n = 4, mean ± SD). (B) Collagen type XI delays CAF-mediated collagen matrix remodeling. CAFs were embedded in a matrix of collagen type I, collagen type XI or a mix of both collagens at a ratio of 19:1 and 3:1 (collagen type I:collagen type XI), and allowed to contract the matrix for 24 h. Area of the collagen matrices has been measured at 5 and 24 h. Statistics were performed using a Mann–Whitney test (n = 8, mean ± SD). (C) Collagen type XI inhibits CAF-mediated lung tumor cell migration. Heterospheroids of CAFs (stained with a green dye) and lung tumor cells (stained with a red dye) were embedded in a matrix of collagen type I or a mix of collagen type I and collagen type XI at a 3:1 ratio. The invasion into the collagen matrices was visualized for 2 days using confocal microscopy, scale bars: 200 µm. Arrows denote tracks in the collagen matrix made by migrating CAFs. The migrated area in the collagen matrices was quantified for CAF (D) and lung tumor cells (E) for the three different heterospheroids presented in C and has been averaged. Minimum and maximum values are indicated in each graph. Statistics were performed using a Mann–Whitney test (n = 8, mean ± SD).