{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:38:20Z","timestamp":1791250700395,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Transforming growth factor beta 1 (TGF\u03b21) 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\u03b21, and active osteoblasts express cognate receptors for TGF\u03b21 (TGF\u03b2RI and TGF\u03b2RII). During malignant osteolysis, TGF\u03b21 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitogenic and prosurvival activities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>Canine osteosarcoma (OS) cells will possess TGF\u03b21 signaling machinery. Blockade of TGF\u03b21 signaling will attenuate pro-tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGF\u03b21 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGF\u03b21 concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Thirty-three dogs with appendicular OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Expression of TGF\u03b21 and its cognate receptors, as well as the biologic effects of TGF\u03b21 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGF\u03b2RI\/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGF\u03b21 concentrations were quantified and correlated with bone resorption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Canine OS cells secrete TGF\u03b21, express cognate receptors, and TGF\u03b21 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGF\u03b2RI\/II, and in OS-bearing dogs, circulating TGF\u03b21 concentrations correlate with urine N-telopeptide excretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Canine OS cells possess TGF\u03b21 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro-tumorigenic signaling loop. As such, TGF\u03b21 inhibitors might impede localized OS progression in dogs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.12348","type":"journal-article","created":{"date-parts":[[2014,3,31]],"date-time":"2014-03-31T06:24:56Z","timestamp":1396247096000},"page":"894-904","source":"Crossref","is-referenced-by-count":22,"title":["Pro-tumorigenic Effects of Transforming Growth Factor Beta 1 in Canine Osteosarcoma"],"prefix":"10.1093","volume":"28","author":[{"given":"R.F.","family":"Portela","sequence":"first","affiliation":[{"name":"University of Illinois Department of Veterinary Clinical Medicine, , Urbana, IL, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.A.","family":"Fadl-Alla","sequence":"additional","affiliation":[{"name":"University of Illinois Department of Veterinary Clinical Medicine, , Urbana, IL, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.C.","family":"Pondenis","sequence":"additional","affiliation":[{"name":"University of Illinois Department of Veterinary Clinical Medicine, , Urbana, IL, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.L.","family":"Byrum","sequence":"additional","affiliation":[{"name":"University of Illinois Department of Veterinary Clinical Medicine, , Urbana, IL, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.D.","family":"Garrett","sequence":"additional","affiliation":[{"name":"University of Illinois Department of Veterinary Clinical Medicine, , Urbana, IL, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.L.","family":"Wycislo","sequence":"additional","affiliation":[{"name":"University of Illinois Department of Pathobiology, , Urbana, IL, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.B.","family":"Borst","sequence":"additional","affiliation":[{"name":"North Carolina State University Department of Population Health and Pathobiology, , Raleigh, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.M.","family":"Fan","sequence":"additional","affiliation":[{"name":"University of Illinois Department of Veterinary Clinical Medicine, , Urbana, IL, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"2026020304383688600_jvim12348-bib-0001","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/ng1001-117","article-title":"TGF-beta signaling in tumor suppression and cancer progression","volume":"29","author":"Derynck","year":"2001","journal-title":"Nat Genet"},{"key":"2026020304383688600_jvim12348-bib-0002","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/1479-5876-10-183","article-title":"TGF-beta - an excellent servant but a bad master","volume":"10","author":"Kubiczkova","year":"2012","journal-title":"J Transl Med"},{"key":"2026020304383688600_jvim12348-bib-0003","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1083\/jcb.110.4.1361","article-title":"Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin","volume":"110","author":"Lyons","year":"1990","journal-title":"J Cell Biol"},{"key":"2026020304383688600_jvim12348-bib-0004","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1101\/gad.14.2.163","article-title":"Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis","volume":"14","author":"Yu","year":"2000","journal-title":"Genes Dev"},{"key":"2026020304383688600_jvim12348-bib-0005","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1083\/jcb.124.1.171","article-title":"Latent transforming growth factor-beta 1 associates to fibroblast extracellular matrix via latent TGF-beta binding protein","volume":"124","author":"Taipale","year":"1994","journal-title":"J Cell Biol"},{"key":"2026020304383688600_jvim12348-bib-0006","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1016\/S0021-9258(18)32345-7","article-title":"Transforming growth factor-beta in human platelets. 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