Promoting roles of the secreted frizzled-related protein 2 as a Wnt agonist in lung cancer cells

Abstract

The secreted frizzled-related protein 2 (SFRP2) plays a pivotal role in the Wnt pathway, however, it functions as an agonist or an antagonist is still controversial. We profiled SFRP2 expression in several lung cancer cell lines, and found that A549 and 95-D exhibited the lowest and the highest level of SFRP2, respectively. Then we employed the SFRP2-overexpressing plasmid and siRNA to transfect A549 and 95-D cells, respectively. Through MTT assays, we found that SFRP2 knockdown inhibited cell proliferation, and halted the 95-D cells in G1 phase of the cell cycle by downregulation of CCND1 and CDK4, indicating that SFRP2 has the ability of promoting lung cancer cell proliferation. We further checked the cell properties of migration and invasion, using wound scratch assay and Transwell assays. The data showed decreased migrated and invasive 95-D cells after SFRP2 knockdown, and the observations were the opposite in the overexpressing model, implying that SFRP2 promoted lung cancer cell invasion. Moreover, the canonical Wnt pathway was also studied through detection of β-catenin by western blotting. In the SFRP2 overexpressing model, A549 cells presented stronger expression of β-catenin compared with controls, while it was the opposite in 95-D cells. These results suggested that SFRP2 serves as a Wnt agonist in lung cancer cells. Together, the findings of this study implied that SFRP2 is not only an agonist of Wnt pathway, but also a cancer promoting protein for lung cancer, indicating SFRP2 as a promising therapeutic target for lung cancer treatment.

Frizzled-5: a high affinity receptor for secreted frizzled-related protein-2 activation of nuclear factor of activated T-cells c3 signaling to promote angiogenesis

“…To clarify whether SFRP2 increases or decreases as tumors progress, we previously found that SFRP2 signal intensity increased as a function of tumor volume using SFRP2-targeted molecular imaging of a mouse tumor in vivo [33]. Other studies confirmed our observation showing that overexpression of SFRP2 increases angiogenesis and tumor growth in vitro and in vivo , [8,9,4,6,34,1,7,2,3]. Furthermore, antagonizing SFRP2 with a monoclonal antibody inhibits tumor growth in vivo [10], which establishes the preponderance of evidence that SFRP2 stimulates, rather than suppresses, tumor growth.…”

“…The preponderance of in vivo evidence supports that SFRP2 stimulates tumor growth. Gain of function studies have shown that SFRP2 strongly promotes tumor growth of intracranial glioma [1], renal cell carcinoma [2], lung cancer [3], melanoma [4], and osteosarcoma [5]. Overexpression of transfected SFRP2 in MCF7 breast adenocarcinoma cells increased their resistance to apoptotic signals in vitro [6].…”

Inhibitory Effects and Anti-Invasive Activities of Trehalose Liposomes on the Proliferation of Lung Carcinoma Cells

“…Interestingly, the anti-invasive effects of DMTreC14 were observed at low concentrations (40 μM) without affecting growthinhibition. Actin cytoskeleton dynamics, such as lamellipodia and filopodia formation on the surface of tumor cells plays an important role in the invasion and migration into the surrounding tissue [18][19][20][21][22]. The treatment with DMTreC14 drastically inhibited the filopodia formation in A549 cells.…”

“…By the way, filopodia formation on the surface of tumor cells plays an important role in the invasion and migration into the surrounding tissue [18][19][20]. Accordingly, the suppression effects of DMTreC14 on the filopodia formation of A549 cells were observed by confocal laser microscopy.…”

Apoptotic and Anti-invasive Effects of Hybrid Liposomes without Drugs against Human Breast Cancer Cells In Vitro

“…The antimigration effects of HL were scrutinized at low concentrations (200 μM) without affecting growth-inhibition below IC 50 values (200 μM). Additionally, pseudopodium development on the exterior of tumour cells has a chief responsibility in the invasion and migration into the neighbouring tissue [18][19][20]. The suppression actions of HL on the pseudopodium formation of MCF-7 cells were scrutinised by using confocal laser microscopy ( Figure 4).…”