title: Bone Morphogenetic Proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion.
abstract: Bone Morphogenetic Proteins (BMPs) are secreted cytokines that are part of the Transforming Growth Factor β (TGFβ) superfamily. BMPs have been shown to be highly expressed in human breast cancers, and loss of BMP signaling in mammary carcinomas has been shown to accelerate metastases. Interestingly, other work has indicated that stimulation of dermal fibroblasts with BMP can enhance secretion of pro-tumorigenic factors. Furthermore, treatment of carcinoma-associated fibroblasts (CAFs) derived from a mouse prostate carcinoma with BMP4 was shown to stimulate angiogenesis. We sought to determine the effect of BMP treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases (MMPs) were found to be upregulated in response to BMP4 treatment. Fibroblasts that were stimulated with BMP4 were found to enhance mammary carcinoma cell invasion, and these effects were inhibited by a BMP receptor kinase antagonist. Treatment with BMP in turn elevated pro-tumorigenic secreted factors such as IL-6 and MMP-3. These experiments demonstrate that BMP may stimulate tumor progression within the tumor microenvironment.
authors.affiliation: Department of Cancer Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Philip
authors.initials: P
authors.lastname: Owens
authors.forename: Hannah
authors.initials: H
authors.lastname: Polikowsky
authors.forename: Michael W
authors.initials: MW
authors.lastname: Pickup
authors.forename: Agnieszka E
authors.initials: AE
authors.lastname: Gorska
authors.forename: Bojana
authors.initials: B
authors.lastname: Jovanovic
authors.forename: Aubie K
authors.initials: AK
authors.lastname: Shaw
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Novitskiy
authors.forename: Charles C
authors.initials: CC
authors.lastname: Hong
authors.forename: Harold L
authors.initials: HL
authors.lastname: Moses
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D015850:Interleukin-6; D019278:Matrix Metalloproteinase 3