Portela R F, Fadl-Alla B A, Pondenis H C, Byrum M L, Garrett L D, Wycislo K L, Borst L B, Fan T M
Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL, NC.
J Vet Intern Med. 2014 May-Jun;28(3):894-904. doi: 10.1111/jvim.12348. Epub 2014 Mar 31.
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 mitogenic and prosurvival activities.
Canine osteosarcoma (OS) cells will possess TGFβ1 signaling machinery. Blockade of TGFβ1 signaling will attenuate pro-tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGFβ1 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGFβ1 concentrations.
Thirty-three dogs with appendicular OS.
Expression of TGFβ1 and its cognate receptors, as well as the biologic effects of TGFβ1 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGFβRI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGFβ1 concentrations were quantified and correlated with bone resorption.
Canine OS cells secrete TGFβ1, express cognate receptors, and TGFβ1 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGFβRI/II, and in OS-bearing dogs, circulating TGFβ1 concentrations correlate with urine N-telopeptide excretion.
Canine OS cells possess TGFβ1 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro-tumorigenic signaling loop. As such, TGFβ1 inhibitors might impede localized OS progression in dogs.
转化生长因子β1（TGFβ1）是一种多效性细胞因子，通过诱导成骨细胞增殖、迁移和血管生成，促进骨骼修复性重塑。有机骨基质是潜伏性TGFβ1在体内的最大储存库，活跃的成骨细胞表达TGFβ1的同源受体（TGFβRI和TGFβRII）。在恶性骨溶解过程中，TGFβ1从被侵蚀的骨基质中释放出来，并通过其促有丝分裂和促生存活性促进亲骨性实体瘤的局部进展。
犬骨肉瘤（OS）细胞将拥有TGFβ1信号传导机制。阻断TGFβ1信号将减弱OS细胞中的促肿瘤活性。自然发生的原发性OS样本将表达同源TGFβ1受体；在患有OS的犬中，局灶性恶性骨溶解将导致循环中TGFβ1浓度升高。
33只患有四肢OS的犬。
在OS细胞中对TGFβ1及其同源受体的表达以及TGFβ1阻断的生物学效应进行了表征。通过免疫组织化学对10个自发性OS样本的TGFβRI/II表达进行了表征。对33只患有OS的犬，定量测定血浆TGFβ1浓度，并将其与骨吸收相关联。
犬OS细胞分泌TGFβ1，表达同源受体，TGFβ1信号阻断可降低细胞增殖、迁移和血管内皮生长因子分泌。自然发生的OS样本大量且均匀地表达TGFβRI/II，在患有OS的犬中，循环TGFβ1浓度与尿N-端肽排泄相关。
犬OS细胞拥有TGFβ1信号传导机制，这可能允许建立自分泌和旁分泌促肿瘤信号回路。因此，TGFβ1抑制剂可能会阻碍犬局部OS的进展。
