TIMP-2 growth-stimulatory activity: A concentration-and cell type-specific response in the presence of insulin

Jeffrey A. Nemeth, Abdur Rafe, Marianne Steiner, Charles L. Goolsby*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

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 languageEnglish (US)
Pages (from-to)110-115
Number of pages6
JournalExperimental Cell Research
Volume224
Issue number1
DOIs
StatePublished - Apr 10 1996

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'TIMP-2 growth-stimulatory activity: A concentration-and cell type-specific response in the presence of insulin'. Together they form a unique fingerprint.

Cite this