Recombinant latent transforming growth factor beta 1 has a longer plasma half-life in rats than active transforming growth factor beta 1, and a different tissue distribution.

Wakefield, Lalage M.; Winokur, Thomas S.; Hollands, Robin S.; Christopherson, Kent W.; Levinson, Arthur D.; Sporn, Michael B.

doi:10.1172/jci114932

Cited by 300 publications

(175 citation statements)

References 26 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…TGF-fl has a o, imilar half-life of 2.2 rain in rats [13] and is cleared in the same way as PDGF by binding to cx~-macroglobulin [14,15]. In contrast, recombinant latent TGF-fl does not associate with 0:2-macroglobulin and has an extended plasma half-life of slightly more than 100 rain in rats [16], which is somewhat closer to that which we determined for PD-ECGF.…”

Section: Discussionsupporting

confidence: 74%

Platelet‐derived endothelial cell growth factor Pharmacokinetics, organ distribution and degradation after intravenous administration in rats

et al. 1992

View full text Add to dashboard Cite

Platelet-denved endothelial cell growth factor (PD-ECGF) stimulaten chcmotaxts of endothehal cells in wtro and has angiogenic acttvity m vtvo. Recenti2¢ PD-ECGF was shown to have thymidine phosphorylase activity. In order to ~tudy po5,~tble thcral~ntte appheation~ of PD-I:COF we used a rat model to determine it~ pharmacokinettc~ and tt~sue dtstnbuttoa after intravenou~ injection.[~2~I]PD-ECGF dtsappeared from the plasma in a btphasic manner, with estimated distribution and ehmmation half-hves of 17 rain and 7 h, respectively. PD-ECGF was metabolized tn the liver, excreted via the bde, and not accumulat~ an any organ system. The stability and long half-hfe in the cireulatton, together wah the specificity for endothelial cell.~, suggest that PD-ECGF may be useful as a therapeutic agent to stimulate re-endolhelialization m vtvo, or, in vtcw of its thym~dine phosphoryla~e activity, in chemotherapy, by decrcasmg the pool of available thymidine.

show abstract

Section: Discussionsupporting

confidence: 74%

Platelet‐derived endothelial cell growth factor Pharmacokinetics, organ distribution and degradation after intravenous administration in rats

et al. 1992

View full text Add to dashboard Cite

show abstract

“…Time point analyses demonstrated that IL-1a mRNA upregulation was rapid, occurring within 30 min of TGF-b exposure, peaked at 1 h and was completely absent within 24 h (data not shown). The kinetics of this gene regulation are consistent with the known half lives of TGF-b and IL-1a mRNA and the fact that TGF-b containing medium needs to be replenished daily to obtain maximum mitogenic stimulation (Turner et al, 1989;Wakefield et al, 1990). To determine if this effect was unique to MCF-10A cells or more broadly applicable, we examined two additional human cell lines previously described to have a growth stimulatory response to TGF-b.…”

mentioning

confidence: 62%

Interleukin-1 alpha mediates the growth proliferative effects of transforming growth factor-beta in p21 null MCF-10A human mammary epithelial cells

et al. 2006

View full text Add to dashboard Cite

Transforming growth factor-b type 1 (TGF-b) has been implicated as both a tumor suppressor and a tumor promoter in many solid epithelial cancers. We have previously demonstrated that the cyclin dependent kinase (CDK) inhibitor p21 acts as a molecular switch in determining a growth inhibitory versus growth proliferative response to TGF-b in the spontaneously immortalized human mammary epithelial cell line MCF-10A. We now demonstrate that this proliferative effect of TGF-b is mediated through the proinflammatory cytokine, interleukin-1a (IL-1a). Using gene expression array analysis, we identified IL-1a as a cytokine specifically upregulated only in cells lacking p21 and only upon TGF-b stimulation. Cell proliferation assays verified that recombinant IL-1a was capable of inducing a growth proliferative response in p21 null MCF-10A cells, while neutralizing antibodies against IL-1a prevented the growth proliferative effects of TGF-b. Mechanistically, both the CDK and proliferating cell nuclear antigen (PCNA) inhibitory functions of p21 were responsible for preventing TGF-b induced cell proliferation, but only PCNA inhibition by p21 regulated IL-1a gene expression. These studies demonstrate a novel role for IL-1a in mediating a proliferative response to TGF-b signaling, and suggest that therapies directed against IL-1a could abate the growth proliferative effects of TGF-b without compromising its tumor suppressive function.

show abstract

“…This would be in agreement with the latent TGF␤1 complex representing a circulating form of TGF␤1. In support of this idea, it has been shown that the latent complex of TGF␤1 has a serum half-life of 2 h as opposed to a half-life of 3 min observed for the mature active growth factor (15). Formation of latent complexes could thus switch TGF␤ from an autocrine/paracrine mode of action to a more 3.…”

Section: Lap Forms a Molecular Complex With Immobilized Tgf␤1-mentioning

confidence: 96%

“…Indeed, several studies suggest that LAP is a potent inhibitor of bioactive TGF␤ both in vitro and in vivo (6,14). Furthermore, formation of latent complexes increases plasma TGF␤1 half-life about 50-fold (15). Moreover, LAP interacts with the mannose 6-phosphate receptor that has been shown to be required for cellular activation of latent TGF␤1 (16); thus LAP could potentially contribute to enhanced and targeted TGF␤ activity.…”

mentioning

confidence: 99%

Analysis of Small Latent Transforming Growth Factor-β Complex Formation and Dissociation by Surface Plasmon Resonance

Bailly

Brand

Chambaz

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

Transforming growth factor-␤ (TGF␤) is a pluripotent regulator of cell growth and differentiation. The growth factor is expressed as a latent complex that must be converted to an active form before interacting with its ubiquitous high affinity receptors. This conversion involves the release of the mature TGF␤ through disruption of the noncovalent interactions with its propeptide or latency associated protein (LAP). Complex formation or dissociation between LAP and TGF␤ plays a very important role in TGF␤ biological activity at different steps. To further characterize the kinetic parameters of this interaction, we have employed surface plasmon resonance biosensor methodology. Using this technique, we observed real time association of LAP with mature TGF␤1. The complex formation showed an equilibrium K d around 3-7 nM. Furthermore, we observed dissociation of the complex in the presence of extreme pH, chaotropic agents, or plasmin, confirming their effects on TGF␤ activation. The same approach was used to examine whether latent TGF␤1 could interact with thrombospondins, previously described as activators of latent TGF␤. Using this method, we could not detect any direct interaction of thrombospondins with either LAP alone, TGF␤1 alone, or the small latent TGF␤1 complex. This suggests that activation of latent TGF␤1 complex by thrombospondins is through an indirect mechanism.

show abstract

Recombinant latent transforming growth factor beta 1 has a longer plasma half-life in rats than active transforming growth factor beta 1, and a different tissue distribution.

Cited by 300 publications

References 26 publications

Platelet‐derived endothelial cell growth factor Pharmacokinetics, organ distribution and degradation after intravenous administration in rats

Platelet‐derived endothelial cell growth factor Pharmacokinetics, organ distribution and degradation after intravenous administration in rats

Interleukin-1 alpha mediates the growth proliferative effects of transforming growth factor-beta in p21 null MCF-10A human mammary epithelial cells

Analysis of Small Latent Transforming Growth Factor-β Complex Formation and Dissociation by Surface Plasmon Resonance

Contact Info

Product

Resources

About