scholarly journals Syndecan-4 Promotes Epithelial Tumor Cells Spreading and Regulates the Turnover of PKCα Activity under Mechanical Stimulation on the Elastomeric Substrates

2015 ◽  
Vol 36 (4) ◽  
pp. 1291-1304 ◽  
Author(s):  
Chun-Ping Huang ◽  
Chao-Min Cheng ◽  
Hong-Lin Su ◽  
Yi-Wen Lin
Keyword(s):  
Mechanical Stress ◽  
Tumor Cells ◽  
Focal Adhesion ◽  
Mechanical Stimulation ◽  
Binding Motif ◽  
Epithelial Tumor ◽  
Cell Contractility ◽  
Myosin Light Chain 2 ◽  
Epithelial Tumor Cells ◽  
Time Courses

Background: Heparan sulfate proteoglycans (HSPGs) at the cell surface play an important role in cell adhesion, spreading, formation of focal adhesion complexes (FACs), and sensing mechanical stress. Syndecans are members of the HSPGs family and are highly expressed in various tumor cells. Syndecan-4 (SDC4) is a unique member of syndecans that activates protein kinase C alpha (PKCα). However, syndecan-4 in tumor cells development is not clear when receiving mechanical stress. Aims: Here we investigate the role of syndecan-4 in tumor cells spreading and its downstream kinases under mechanical stimulation. Methods: Epithelial tumor cells were seeded onto elastomeric polydimethylsiloxane (PDMS) membranes coated with poly-L-lysine (Pl), fibronectin (Fn), or anti-SDC4 antibody and stretched with a modified pressure-driven cell-stretching (PreCS) device. Results: When cells received mechanical stimulation, engagement of syndecan-4 promoted the phosphorylation of focal adhesion kinase (FAK) at tyrosine 397 and PKCα at serine 657. Furthermore, we analyzed the cell contractility marker—myosin light chain 2 (MLC2) in 30 min time courses. The levels of phosphorylated MLC2 at serine19 were augmented through ligations of syndecan-4 but not integrin binding motif (RGD) at 10 min mechanical stimulation and were suppressed at 30 min and this phenomenon was associated with the activity of PKCα. Conclusion: Our data demonstrate that syndecan-4 is essential for transmitting the mechanotransduction signals via activation of PKCα and is important for tumor cells spreading, assembly of actin cytoskeleton and cell contractility.

Methodological Analysis of Immunocytochemical Screening for Disseminated Epithelial Tumor Cells in Bone Marrow

1994 ◽  
Vol 3 (3) ◽  
pp. 165-173 ◽  
Author(s):  
KLAUS PANTEL ◽  
GÜNTER SCHLIMOK ◽  
MATTHIAS ANGSTWURM ◽  
DOROTHEA WECKERMANN ◽  
WERNER SCHMAUS ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Epithelial Tumor ◽  
Epithelial Tumor Cells

scholarly journals Fibronectin-Expressing Mesenchymal Tumor Cells Promote Breast Cancer Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2553 ◽  
Author(s):  
Brian H. Jun ◽  
Tianqi Guo ◽  
Sarah Libring ◽  
Monica K. Chanda ◽  
Juan Sebastian Paez ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cell Tracking ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Tumor ◽  
Minority Population ◽  
Metastatic Niche ◽  
Epithelial Tumor ◽  
Epithelial Tumor Cells ◽  
Cell Series

Tumor metastasis is connected to epithelial-mesenchymal heterogeneity (EMH) and the extracellular matrix (ECM) within the tumor microenvironment. Mesenchymal-like fibronectin (FN) expressing tumor cells enhance metastasis within tumors that have EMH. However, the secondary tumors are primarily composed of the FN null population. Interestingly, during tumor cell dissemination, the invasive front has more mesenchymal-like characteristics, although the outgrowths of metastatic colonies consist of a more epithelial-like population of cells. We hypothesize that soluble FN provided by mesenchymal-like tumor cells plays a role in supporting the survival of the more epithelial-like tumor cells within the metastatic niche in a paracrine manner. Furthermore, due to a lower rate of proliferation, the mesenchymal-like tumor cells become a minority population within the metastatic niche. In this study, we utilized a multi-parametric cell-tracking algorithm and immunoblotting to evaluate the effect of EMH on the growth and invasion of an isogenic cell series within a 3D collagen network using a microfluidic platform. Using the MCF10A progression series, we demonstrated that co-culture with FN-expressing MCF10CA1h cells significantly enhanced the survival of the more epithelial MCF10CA1a cells, with a two-fold increase in the population after 5 days in co-culture, whereas the population of the MCF10CA1a cells began to decrease after 2.5 days when cultured alone (p < 0.001). However, co-culture did not significantly alter the rate of proliferation for the more mesenchymal MCF10CA1h cells. Epithelial tumor cells not only showed prolonged survival, but migrated significantly longer distances (350 µm compared with 150 µm, respectively, p < 0.01) and with greater velocity magnitude (4.5 µm/h compared with 2.1 µm/h, respectively, p < 0.001) under co-culture conditions and in response to exogenously administered FN. Genetic depletion of FN from the MCF10CA1h cells resulted in a loss of survival and migration capacity of the epithelial and mesenchymal populations. These data suggest that mesenchymal tumor cells may function to support the survival and outgrowth of more epithelial tumor cells within the metastatic niche and that inhibition of FN production may provide a valuable target for treating metastatic disease.

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