Parallel inhibition of cell growth and induction of cell migration and invasion in breast cancer cells by bone morphogenetic protein 4

2010 ◽  
Vol 124 (2) ◽  
pp. 377-386 ◽  
Author(s):  
Johanna M. Ketolainen ◽  
Emma-Leena Alarmo ◽  
Vilppu J. Tuominen ◽  
Anne Kallioniemi
2017 ◽  
Vol 28 ◽  
pp. xi26
Author(s):  
B. Al-Sulaiti ◽  
A. Naser ◽  
R. Thomas ◽  
G. Al-Khadairi ◽  
J. Decock

2015 ◽  
Vol 37 (4) ◽  
pp. 1271-1278 ◽  
Author(s):  
Xuexiang Ying ◽  
Yunpo Sun ◽  
Pingqing He

Background/Aims: Bone morphogenetic protein-7 (BMP7) has been shown to reduce the severity of injury-induced fibrosis through counteracting the fibrotic effects of transforming growth factor β 1 (TGFβ1). However, this model in the carcinogenesis of breast cancer is unknown. Methods: We analyzed the effects of BMP7 and TGFβ1 on gene transcripts and protein levels of EMT-related factors in breast cancer cells by RT-qPCR and Western blot, respectively. The effects of BMP7 and TGFβ1 on cell invasiveness and migration were evaluated by scratch wound healing assay and transwell cell migration assay. The cell growth was measured by MTT assay. Results: BMP7 did not alter the TGFβ1-stimulated phosphorylation of TGFβ receptor, but significantly inhibited the TGFβ1-activated epithelial-mesenchymal transition (EMT)-related genes in breast cancer cells, resulting in a significant reduction in TGFβ1-triggered cell growth and cell metastasis. Conclusion: Our data suggest that besides being a well-known antagonist for TGFβ1 in fibrosis, BMP7 may also antagonize TGFβ1 in tumorigenesis-associated EMT in breast cancer. Thus, BMP7 may be a promising therapeutic target for treating breast cancer.


2021 ◽  
Vol 50 (10) ◽  
pp. 3015-3033
Author(s):  
Wee Yee Tan ◽  
Boon Yin Khoo ◽  
Ai Lan Chew

Atypical chemokine receptor proteins are termed ‘decoy proteins’ as their binding to the respective ligands does not lead to a typical signaling pathway but intercepts the action of chemokines. This method of chemokine activity regulation may also function in tumor suppression. D6 and DARC (Duffy Antigen Receptor for Chemokines) have been reported as decoy chemokine receptors in cancer studies. Purified Pichia-expressed D6 and DARC, produced in-house, were used in cell-based studies to test their biological activities. Cell viability tests showed that recombinant D6 and DARC did not affect cell viability significantly, suggesting that they were not involved in breast cancer cell death. Wound healing assays showed that the presence of recombinant D6 or DARC at 10 µg/mL optimally inhibited the migration of breast cancer cells. ELISA showed an inverse relationship between the recombinant proteins and CCL2 levels in the treated cells. Migration assay using Boyden chamber demonstrated the function of the recombinant proteins in inhibiting chemotaxis activity of treated cells. Invasion assay showed the ability of the recombinant proteins in inhibiting the invasion property of treated cells. Comparison of single and combinatorial effects of the recombinant proteins showed that the combination of D6 and DARC at a 1:1 ratio (10 µg/mL) is most effective in reducing CCL2 levels and inhibiting the migration and invasion of treated cells. It was shown that the purified Pichia-expressed recombinant D6 and DARC are the negative regulators of breast cancer cell migration and invasion, and the inhibition effects were greater when they were used in combination.


2016 ◽  
Vol 36 (10) ◽  
pp. 1509-1525 ◽  
Author(s):  
Chanèle Cyr-Depauw ◽  
Jason J. Northey ◽  
Sébastien Tabariès ◽  
Matthew G. Annis ◽  
Zhifeng Dong ◽  
...  

ShcA is an important mediator of ErbB2- and transforming growth factor β (TGF-β)-induced breast cancer cell migration, invasion, and metastasis. We show that in the context of reduced ShcA levels, the bone morphogenetic protein (BMP) antagonist chordin-like 1 (Chrdl1) is upregulated in numerous breast cancer cells following TGF-β stimulation. BMPs have emerged as important modulators of breast cancer aggressiveness, and we have investigated the ability of Chrdl1 to block BMP-induced increases in breast cancer cell migration and invasion. Breast cancer-derived conditioned medium containing elevated concentrations of endogenous Chrdl1, as well as medium containing recombinant Chrdl1, suppresses BMP4-induced signaling in multiple breast cancer cell lines. Live-cell migration assays reveal that BMP4 induces breast cancer migration, which is effectively blocked by Chrdl1. We demonstrate that BMP4 also stimulated breast cancer cell invasion and matrix degradation, in part, through enhanced metalloproteinase 2 (MMP2) and MMP9 activity that is antagonized by Chrdl1. Finally, high Chrdl1 expression was associated with better clinical outcomes in patients with breast cancer. Together, our data reveal that Chrdl1 acts as a negative regulator of malignant breast cancer phenotypes through inhibition of BMP signaling.


2015 ◽  
Vol 12 (2) ◽  
pp. 3121-3126 ◽  
Author(s):  
HUI LI ◽  
JIASHUN LUO ◽  
BIN XU ◽  
KAIJUN LUO ◽  
JUAN HOU

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