{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:52:44Z","timestamp":1791337964023,"version":"4.3.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"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":[[2007,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bone metastases develop in \u02dc30% of patients with RCC, and the mechanisms responsible for this phenomenon are unknown. We found that TGF-\u03b21 stimulation of RCC bone metastasis cells promotes tumor growth and bone destruction possibly by stimulating paracrine interactions between tumor cells and the bone.<\/jats:p>\n               <jats:p>Introduction: Bone metastasis is a frequent complication and causes marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the specific mechanisms of RCC interaction with bone have been scarcely studied despite the inability to prevent or effectively treat bone metastasis. Bone is a reservoir for various growth factors including the pleiotropic cytokine TGF-\u03b21. TGF-\u03b21 has been shown to have tumor-supportive effects on advanced cancers and evidence suggests its involvement in promoting the development of breast cancer bone metastasis. Here, we studied the potential role of TGF-\u03b21 in the growth of RCC bone metastasis (RBM).<\/jats:p>\n               <jats:p>Materials and Methods: To inhibit TGF-\u03b21 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-\u03b2RII cDNA were generated. The in vivo effect of TGF-\u03b21 on RBM tumor growth and osteolysis was determined by histological and radiographic analysis, respectively, of athymic nude mice after intratibial injection of parental, empty vector, or DN RBM cells. The in vitro effect of TGF-\u03b21 on RBM cell growth was determined after TGF-\u03b21 treatment by MTT assay.<\/jats:p>\n               <jats:p>Results: TGF-\u03b21 and the TGF-\u03b2 receptors I and II (TGF-\u03b2RI\/II) were consistently expressed in both RBM tissues and cell lines. Inhibition of TGF-\u03b21 signaling in RBM cells significantly reduced tumor establishment and osteolysis observed in vivo after injection into the murine tibia, although no effect on tumor establishment was observed after injection of RBM cells subcutaneously or into the renal subcapsule. Treatment of five RBM cell lines with TGF-\u03b21 in vitro either had no effect (2\/5) or resulted in a significant inhibition (3\/5) of cell growth, suggesting that TGF-\u03b21 may promote RBM tumor growth indirectly in vivo.<\/jats:p>\n               <jats:p>Conclusions: TGF-\u03b21 stimulation of RBM cells plays a role in promoting tumor growth and subsequent osteolysis in vivo, likely through the initiation of tumor-promoting paracrine interactions between tumor cells and the bone microenvironment. These data suggest that inhibition of TGF-\u03b21 signaling may be useful in the treatment of RBM.<\/jats:p>","DOI":"10.1359\/jbmr.061005","type":"journal-article","created":{"date-parts":[[2006,10,10]],"date-time":"2006-10-10T13:43:11Z","timestamp":1160487791000},"page":"37-44","source":"Crossref","is-referenced-by-count":75,"title":["TGF-\u03b2 Promotes the Establishment of Renal Cell Carcinoma Bone Metastasis"],"prefix":"10.1093","volume":"22","author":[{"given":"Scott L","family":"Kominsky","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Doucet","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Brady","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy L","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020319214603300_bib1","first-page":"379","article-title":"The skeletal metastatic complications of renal cell carcinoma","volume":"19","author":"Zekri","year":"2001","journal-title":"Int J Oncol"},{"key":"2024020319214603300_bib2","first-page":"98","article-title":"The distribution of secondary growths in cancer of the breast. 1889","volume":"8","author":"Paget","year":"1989","journal-title":"Cancer Metastasis Rev"},{"key":"2024020319214603300_bib3","doi-asserted-by":"crossref","first-page":"12665","DOI":"10.1016\/S0021-9258(18)67143-1","article-title":"Growth factors in bone matrix. 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