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Pro-tumorigenic effects of transforming growth factor beta 1 in canine osteosarcoma.


ABSTRACT: Transforming growth factor beta 1 (TGF?1) is a pleiotropic cytokine that contributes to reparative skeletal remodeling by inducing osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the largest bodily reservoir for latent TGF?1, and active osteoblasts express cognate receptors for TGF?1 (TGF?RI and TGF?RII). During malignant osteolysis, TGF?1 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitogenic and prosurvival activities.Canine osteosarcoma (OS) cells will possess TGF?1 signaling machinery. Blockade of TGF?1 signaling will attenuate pro-tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGF?1 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGF?1 concentrations.Thirty-three dogs with appendicular OS.Expression of TGF?1 and its cognate receptors, as well as the biologic effects of TGF?1 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGF?RI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGF?1 concentrations were quantified and correlated with bone resorption.Canine OS cells secrete TGF?1, express cognate receptors, and TGF?1 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGF?RI/II, and in OS-bearing dogs, circulating TGF?1 concentrations correlate with urine N-telopeptide excretion.Canine OS cells possess TGF?1 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro-tumorigenic signaling loop. As such, TGF?1 inhibitors might impede localized OS progression in dogs.

SUBMITTER: Portela RF 

PROVIDER: S-EPMC4895458 | biostudies-literature | 2014 May-Jun

REPOSITORIES: biostudies-literature

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Pro-tumorigenic effects of transforming growth factor beta 1 in canine osteosarcoma.

Portela R F RF   Fadl-Alla B A BA   Pondenis H C HC   Byrum M L ML   Garrett L D LD   Wycislo K L KL   Borst L B LB   Fan T M TM  

Journal of veterinary internal medicine 20140331 3


<h4>Background</h4>Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that contributes to reparative skeletal remodeling by inducing osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the largest bodily reservoir for latent TGFβ1, and active osteoblasts express cognate receptors for TGFβ1 (TGFβRI and TGFβRII). During malignant osteolysis, TGFβ1 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitoge  ...[more]

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