miRNA-30 family members inhibit breast cancer invasion, osteomimicry, and bone destruction by directly targeting multiple bone metastasis–associated genes

miRNAs are master regulators of gene expression that play key roles in cancer metastasis. During bone metastasis, metastatic tumor cells must rewire their biology and express genes that are normally expressed by bone cells (a process called osteomimicry), which endow tumor cells with full competence for outgrowth in the bone marrow. Here, we establish miR-30 family members miR-30a, miR-30b, miR-30c, miR-30d, and miR-30e as suppressors of breast cancer bone metastasis that regulate multiple pathways, including osteomimicry. Low expression of miR-30 in primary tumors from patients with breast cancer were associated with poor relapse-free survival. In addition, estrogen receptor (ER)-negative/progesterone receptor (PR)-negative breast cancer cells expressed lower miR-30 levels than their ER/PR-positive counterparts. Overexpression of miR-30 in ER/PR-negative breast cancer cells resulted in the reduction of bone metastasis burden in vivo. In vitro, miR-30 did not affect tumor cell proliferation, but did inhibit tumor cell invasion. Furthermore, overexpression of miR-30 restored bone homeostasis by reversing the effects of tumor cell–conditioned medium on osteoclastogenesis and osteoblastogenesis. A number of genes associated with osteoclastogenesis stimulation (IL8, IL11), osteoblastogenesis inhibition (DKK-1), tumor cell osteomimicry (RUNX2, CDH11), and invasiveness (CTGF, ITGA5, ITGB3) were identified as targets for repression by miR-30. Among these genes, silencing CDH11 or ITGA5 in ER-/PR-negative breast cancer cells recapitulated inhibitory effects of miR-30 on skeletal tumor burden in vivo. Overall, our findings provide evidence that miR-30 family members employ multiple mechanisms to impede breast cancer bone metastasis and may represent attractive targets for therapeutic intervention. Significance: These findings suggest miR-30 family members may serve as an effective means to therapeutically attenuate metastasis in triple-negative breast cancer

Approche de transfert de gènes, chez le poulet, par manipulation in vitro des cellules germinales primordiales (CGPs). Utilisation de vecteurs rétroviraux dérivés des virus ALSV (Avian Leukosis and Sarcoma Viruses)

*INRA, laboratoire des vecteurs rétroviraux, Villeurbanne Diffusion du document : INRA, laboratoire des vecteurs rétroviraux, Villeurbanne Diplôme : Dr. d'Universit

Politische, häusliche und religiöse Alterthümer der Hebräer

hrsg. von Joseph Franz Allioli. Unter Mitw. von Lorenz Clem. Gratz ...In Fraktu

Use of gonadal primordial germ cells (PGCs) as tools for gene transfer in chickens

International audienc

Biblische Erd- und Länderkunde

hrsg. von Joseph Franz Allioli. Unter Mitw. von Lorenz Clem. Gratz ...In Fraktu

Renewal of thymocyte progenitors and emigration of thymocytes during avian development

The avian thymus is colonized by three waves of hemopoietic progenitors during embryogenesis. An in vivo thymus reconstitution assay based on intrathymic injection of irradiated chicks showed that cells of para-aortic foci were able to differentiate into T lymphocytes, confirming their putative role in the first wave of thymus colonization. This assay was also used to detect and to characterize T cell progenitors from the bone marrow which are involved in the second and third wave of thymus colonization. In the bone marrow, progenitors that differentiated into T cells were found in a subpopulation that expressed the molecules HEMCAM, c-kit and c128. Engraftment of thymus lobes into thymectomized young chick recipients showed that T cell progenitors are replaced in the thymus by subsequent waves of progenitors after hatching. Finally, analysis of thymocyte differentiation suggested that gamma delta and alpha beta T cells migrate from the thymus to the periphery in alternating waves