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 ... -  《-》

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 ... -  《-》

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》

Osteoblast-derived TGF-beta1 stimulates IL-8 release through AP-1 and NF-kappaB in human cancer cells.

Fong YC ，Maa MC ，Tsai FJ ，Chen WC ，Lin JG ，Jeng LB ，Yang RS ，Fu WM ，Tang CH ... -  《-》

Adiponectin increases motility of human prostate cancer cells via adipoR, p38, AMPK, and NF-kappaB pathways.

Prostate cancer is the most commonly diagnosed malignancy in men. Prostate cancer shows a predilection for metastasis to the bone. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and involved in energy homeostasis. The aim of this study was to investigate whether adiponectin is associated with migration of prostate cancer cells. Cancer cells migration activity was examined using the Transwell assay. The p38 and AMPK phosphorylation was examined by using Western blot method. The cell surface expression of integrins was examined by using flow cytometry. The qPCR was used to examine the mRNA expression of integrin. A transient transfection protocol was used to examine NF-kappaB activity. We found that adiponectin increased the migration and the expression of alpha5beta1 integrin of human prostate cancer cells. Adiponectin-mediated migration and integrins expression was attenuated by p38 inhibitor (SB203580), p38 mutant, AMPK siRNA, AMPK inhibitor (araA and compound C). Activations of p38, AMPK and NF-kappaB pathways after adiponectin treatment was demonstrated, and adiponectin-induced expression of integrins and migration activity was inhibited by the specific inhibitor and mutant of p38, AMPK, and NF-kappaB cascades. This study showed for the first time that the adiponectin mediates migration of human prostate cancer cells. One of the mechanisms underlying adiponectin directed migration was transcriptional up-regulation of alpha5beta1 integrin and activation of AdipoR1 receptor, p38, AMPK, and NF-kappaB pathways.

Tang CH ，Lu ME 《-》