EFFECT OF EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA-1 ON GROWTH AND INVASIVE POTENTIALS OF NEWLY ESTABLISHED RAT BLADDER-CARCINOMA CELL-LINES

We established 5 rat bladder cell lines (MYU3L, MYU4, MYU6s, MYKUIL and MYP3). EGF stimulated DNA synthesis of all the cells in monolayer culture, regardless of the number of EGF receptors. In soft agar, only MYU3L formed colonies, and EGF enhanced their growth. However, EGF did not induce the other cells to grow in soft agar. In contrast, TGF-beta1 inhibited the growth of the cells, but a tumorigenic cell and the cells which were established from large in vivo tumors were more resistant than the others to TGF-beta1. We tested the effect of growth factors on the invasive potential of MYP3 cells (non-tumorigenic), MYU3L cells (tumorigenic/highly invasive but not metastatic) from newly established cell lines, and another metastatic cell line, LMC19. MYP3 expressed only a trace amount of 92-kDa gelatinase (MMP-9), whereas MYU3L expressed interstitial collagenase (MMP-1) and MMP-9, and LMC19 expressed 72-kDa gelatinase (MMP-2) and MMP-9. The release of MMP-2 in LMC 1 9 was stimulated by TGF-beta1, but EGF had no effect on the release of any MMPs in either type of cells. These observations suggest that EG F acted as a mitogen on all the cells tested, but did not enhance the malignant phenotype. Further, the loss of responsiveness to the suppressive effect of TGF-beta1 may be an important step toward a malignant phenotype. Some of malignant tumors may utilize TGF-beta1 for enhancing their invasive and metastatic potential. (C) 1993 Wiley-Liss, Inc.