Abstract
In addition to proteinase-inhibitory activities, growth-stimulatory activities have been described for all three known members of the tissue inhibitors of the metalloproteinase (TIMP) family, TIMP-1, TIMP-2, and ChIMP-3, believed to be the chicken homologue of TIMP-3. However, the mechanism by which the TIMPs stimulate cell growth is unclear. In this report we have demonstrated that rTIMP-2 was growth-stimulatory for human foreskin fibroblasts (HSF4, HSF43, HS68), lung adenocarcinoma cells (A549), human melanoma cells (WM115), and the Burkitt's lymphoma cell line RAMOS, and this stimulatory response was concentration-dependent, with the greatest stimulation occurring at 10-30 pM rTIMP-2 in [3H]thymidine incorporation assays and at 20-100 pM in cell growth assays. Normal human colon (18Co) and lung (37Lu) fibroblasts showed no response to rTIMP-2. [3H]-Thymidine incorporation was inhibited by rTIMP-2 treatment in the nonadherent cell line HL60. These studies also demonstrated that for the cell types tested, TIMP-2 alone was insufficient for a growth stimulatory response requiring, at a minimum, the presence of insulin. In the absence of any "co-factor(s)," such as insulin, TIMP-2 treatment was inhibitory.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 110-115 |
| Number of pages | 6 |
| Journal | Experimental Cell Research |
| Volume | 224 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 10 1996 |
Funding
We thank Dr. William G. Stetler Stevenson (NIH, Bethesda, MD) and Dr. Keith Langley (Amgen, Inc., Thousand Oaks, CA) for providing reagents. This work was supported in part by the Veterans Administration (Medical Research Service) and NIH Carcinogenesis Training Program CA09560.
ASJC Scopus subject areas
- Cell Biology