Osteoblasts-derived TGF-beta1 enhance motility and integrin upregulation through Akt, ERK, and NF-kappaB-dependent pathway in human breast cancer cells.

Bone metastases are common complications of breast cancer. Integrins are the major adhesive molecules in mammalian cells. Here we found that osteoblast conditioned medium (OBCM) increased the migration and cell surface expression of beta1 or beta3 integrin in human breast cancer cells (MDA-MB-231 cells). beta1 or beta3 integrin monoclonal antibodies (mAbs) or small interference RNA (siRNA) against beta1 or beta3 integrin inhibited the OBCM-induced increase in the migration of breast cancer cells. Transforming growth factor-beta1 (TGF-beta1) siRNA could remarkably blocked OBCM-induced chemomigration and beta1 and beta3 integrin expression in breast cancer cells. Stimulation of cells with OBCM caused an increase in Akt and extracellular signal-regulated kinase (ERK) phosphorylation in a time-dependent manner. In addition, treatment of MDA-MB-231 cells with phosphatidylinositol 3-kinase inhibitor (LY294002), ERK inhibitor (PD98059), NF-kappaB inhibitor (PDTC), or IkappaB protease inhibitor (TPCK) inhibited OBCM-induced cells migration and integrins expression. Treatment of MDA-MB-231 cells with OBCM induced IkappaB kinase alpha/beta (IKK alpha/beta) phosphorylation, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity. The OBCM-mediated increases in IKK alpha/beta phosphorylation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity were inhibited by LY294002 and PD98059. In addition, TGF-beta1 siRNA also reduced the OBCM-induced ERK, Akt, IKKalpha/beta, IkappaBalpha, and p65 phosphorylation. Taken together, these results suggest that the osteoblast-derived TGF-beta1 acts through Akt and ERK, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the activations of beta1 and beta3 integrins and contributing the migration of breast cancer cell.

Wei YY ，Chen YJ ，Hsiao YC ，Huang YC ，Lai TH ，Tang CH ... -  《-》

Transforming growth factor-beta1 increases cell migration and beta1 integrin up-regulation in human lung cancer cells.

Fong YC ，Hsu SF ，Wu CL ，Li TM ，Kao ST ，Tsai FJ ，Chen WC ，Liu SC ，Wu CM ，Tang CH ... -  《LUNG CANCER》

Osteoblasts-derived BMP-2 enhances the motility of prostate cancer cells via activation of integrins.

Bone metastases are common complications of prostate cancer cells. The bone morphogenetic protein-2 (BMP-2) is constitutively secreted by osteoblasts and plays a key role in bone formation. Integrins are the major adhesive molecules in mammalian cells, and has been associated with cancer cells metastasis to bone. The aim of this study was to investigate whether osteoblast-derived BMP-2 is associated with prostate cancer metastasis. Cancer cells migration activity was examined using the Transwell assay. The ERK and AKT phosphorylation was examined by using Western blot method. The siRNA was used to inhibit the expression of BMP-2. The cell surface expression of integrins was examined by using flow cytometry. A transient transfection protocol was used to examine NF-kappaB activity. We found that osteoblast conditioned medium (OBCM) increased the migration and cell surface expression of beta1 or beta 3 integrin in human prostate cancer cells. beta1 or beta 3 integrin monoclonal antibodies or siRNA against beta1 or beta 3 integrin inhibited the OBCM-induced increase the migration of prostate cancer cells. BMP-2 siRNA specifically reduced the OBCM-induced migration and integrins upregulation. BMP-2 siRNA also suppressed the OBCM-induced ERK, AKT and NF-kappaB activation. This study suggest that the osteoblast-derived BMP-2 act through Akt and ERK, which in turn activates IKK alpha/beta and NF-kappaB, resulting in the activations of beta1 and beta 3 integrins and contributing the migration of prostate cancer cells.

Lai TH ，Fong YC ，Fu WM ，Yang RS ，Tang CH ... -  《-》

BMP-2 increases migration of human chondrosarcoma cells via PI3K/Akt pathway.

Fong YC ，Li TM ，Wu CM ，Hsu SF ，Kao ST ，Chen RJ ，Lin CC ，Liu SC ，Wu CL ，Tang CH ... -  《-》

Stromal cell-derived factor-1 enhances motility and integrin up-regulation through CXCR4, ERK and NF-kappaB-dependent pathway in human lung cancer cells.

Huang YC ，Hsiao YC ，Chen YJ ，Wei YY ，Lai TH ，Tang CH ... -  《BIOCHEMICAL PHARMACOLOGY》