title: The impact of bone morphogenetic protein 4 (BMP4) on breast cancer metastasis in a mouse xenograft model.
abstract: Bone morphogenetic protein 4 (BMP4) is a key regulator of cell proliferation and differentiation. In breast cancer cells, BMP4 has been shown to reduce proliferation in vitro and interestingly, in some cases, also to induce migration and invasion. Here we investigated whether BMP4 influences breast cancer metastasis formation by using a xenograft mouse model. MDA-MB-231 breast cancer cells were injected intracardially into mice and metastasis formation was monitored using bioluminescence imaging. Mice treated with BMP4 developed metastases slightly earlier as compared to control animals but the overall number of metastases was similar in both groups (13 in the BMP4 group vs. 12 in controls). In BMP4-treated mice, bone metastases were more common (10 vs. 7) but adrenal gland metastases were less frequent (1 vs. 5) than in controls. Immunostaining revealed no differences in signaling activation, proliferation rate, blood vessel formation, EMT markers or the number of cancer-associated fibroblasts between the treatment groups. In conclusion, BMP4 caused a trend towards accelerated metastasis formation, especially in bone. More work is needed to uncover the long-term effects of BMP4 and the clinical relevance of these findings.
authors.affiliation: University of Tampere, BioMediTech, Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Ampuja
authors.affiliation: University of Tampere, BioMediTech, Tampere, Finland.
authors.forename: E L
authors.initials: EL
authors.lastname: Alarmo
authors.affiliation: Department of Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: P
authors.initials: P
authors.lastname: Owens
authors.affiliation: University of Tampere, BioMediTech, Tampere, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Havunen
authors.affiliation: Department of Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Gorska
authors.affiliation: Department of Cancer Biology, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Moses
authors.affiliation: University of Tampere, BioMediTech, Tampere, Finland. Electronic address: anne.kallioniemi@uta.fi.
authors.forename: A
authors.initials: A
authors.lastname: Kallioniemi
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000008:administration & dosage* / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D011994:Recombinant Proteins
keywords: BMP4; Bioluminescence imaging; Bone morphogenetic protein; Breast cancer; In vivo metastasis model