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Antimicrobial peptide LL-37 promotes the proliferation and invasion of skin squamous cell carcinoma by upregulating DNA-binding protein A

View Article: PubMed Central - PubMed

ABSTRACT

The antimicrobial peptide LL-37 not only contributes to the host defence against microbial invasion but also regulates immune activity, angiogenesis and cell proliferation. Studies have shown that LL-37 participates in the development of a variety of tumours, such as lung cancer, ovarian cancer, breast cancer and melanoma. However, the role of LL-37 in the development of skin squamous cell carcinoma (SCC) is not clear. The present study used immunohistochemistry to confirm that the expression of human DNA-binding protein A (dbpA) was increased in SCC tissues. After stimulating SCC A341 cells, LL-37 was shown promote the proliferation, migration and invasion of these malignant cells. LL-37 also promoted the upregulation of dbpA mRNA and protein expression. In addition, after using small interfering RNA to silence the normal dbpA expression in these malignant cells, the proliferation and invasion of the tumor cells were significantly reduced. When the NF-κB inhibitor PDTC was used to inhibit the process of LL-37-stimulated cells, it was found that the original upregulated expression of dbpA was downregulated. Overall, the present demonstrated that by upregulating the expression of dbpA, LL-37 can promote the proliferation and invasion of tumour cells, and that this process depends on the NF-κB signalling pathway.

No MeSH data available.


Related in: MedlinePlus

(A) LL-37 induces migration in A431 cells. Serum-starved A431 were treated with LL-37 at 0.05, 0.5 and 5 µg/ml of LL-37 for 12 h, and the cell migration was analysed. (B) LL-37 induces invasion of A431 cells. Serum-starved A431 cells were treated with LL-37 at 0.05, 0.5 and 5 µg/ml of LL-37 for 24 h, and the cell invasion was analysed. Magnification, ×200. The results from three random fields are shown and presented as the mean ± standard deviation. (C) LL-37 promotes the upregulation of dbpA mRNA in A431 cells. Time effect: A431 cells were stimulated with 0.5 µg/ml LL-37 for the specified durations. Dose effects: A431 cells were stimulated with the specified doses of LL-37 for 24 h. DbpA mRNA levels were determined by quantitative polymerase chain reaction. The figure shows the ratio of dbpA mRNA/β-actin mRNA. *P<0.05 vs. control, 0 h or 0 µg/ml. siRNA, small interfering RNA; dbpA, DNA-binding protein A.
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f3-ol-0-0-4865: (A) LL-37 induces migration in A431 cells. Serum-starved A431 were treated with LL-37 at 0.05, 0.5 and 5 µg/ml of LL-37 for 12 h, and the cell migration was analysed. (B) LL-37 induces invasion of A431 cells. Serum-starved A431 cells were treated with LL-37 at 0.05, 0.5 and 5 µg/ml of LL-37 for 24 h, and the cell invasion was analysed. Magnification, ×200. The results from three random fields are shown and presented as the mean ± standard deviation. (C) LL-37 promotes the upregulation of dbpA mRNA in A431 cells. Time effect: A431 cells were stimulated with 0.5 µg/ml LL-37 for the specified durations. Dose effects: A431 cells were stimulated with the specified doses of LL-37 for 24 h. DbpA mRNA levels were determined by quantitative polymerase chain reaction. The figure shows the ratio of dbpA mRNA/β-actin mRNA. *P<0.05 vs. control, 0 h or 0 µg/ml. siRNA, small interfering RNA; dbpA, DNA-binding protein A.

Mentions: Compared with the control group, different concentrations of LL-37 enhanced the migration of the A431 cells after 12 h of culture (P=0.001; Fig. 3A) and the invasiveness of the A431 cells after 24 h of culture (Fig. 3B). The most effective concentration was 0.5 µg/ml (P=0.002).


Antimicrobial peptide LL-37 promotes the proliferation and invasion of skin squamous cell carcinoma by upregulating DNA-binding protein A
(A) LL-37 induces migration in A431 cells. Serum-starved A431 were treated with LL-37 at 0.05, 0.5 and 5 µg/ml of LL-37 for 12 h, and the cell migration was analysed. (B) LL-37 induces invasion of A431 cells. Serum-starved A431 cells were treated with LL-37 at 0.05, 0.5 and 5 µg/ml of LL-37 for 24 h, and the cell invasion was analysed. Magnification, ×200. The results from three random fields are shown and presented as the mean ± standard deviation. (C) LL-37 promotes the upregulation of dbpA mRNA in A431 cells. Time effect: A431 cells were stimulated with 0.5 µg/ml LL-37 for the specified durations. Dose effects: A431 cells were stimulated with the specified doses of LL-37 for 24 h. DbpA mRNA levels were determined by quantitative polymerase chain reaction. The figure shows the ratio of dbpA mRNA/β-actin mRNA. *P<0.05 vs. control, 0 h or 0 µg/ml. siRNA, small interfering RNA; dbpA, DNA-binding protein A.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998069&req=5

f3-ol-0-0-4865: (A) LL-37 induces migration in A431 cells. Serum-starved A431 were treated with LL-37 at 0.05, 0.5 and 5 µg/ml of LL-37 for 12 h, and the cell migration was analysed. (B) LL-37 induces invasion of A431 cells. Serum-starved A431 cells were treated with LL-37 at 0.05, 0.5 and 5 µg/ml of LL-37 for 24 h, and the cell invasion was analysed. Magnification, ×200. The results from three random fields are shown and presented as the mean ± standard deviation. (C) LL-37 promotes the upregulation of dbpA mRNA in A431 cells. Time effect: A431 cells were stimulated with 0.5 µg/ml LL-37 for the specified durations. Dose effects: A431 cells were stimulated with the specified doses of LL-37 for 24 h. DbpA mRNA levels were determined by quantitative polymerase chain reaction. The figure shows the ratio of dbpA mRNA/β-actin mRNA. *P<0.05 vs. control, 0 h or 0 µg/ml. siRNA, small interfering RNA; dbpA, DNA-binding protein A.
Mentions: Compared with the control group, different concentrations of LL-37 enhanced the migration of the A431 cells after 12 h of culture (P=0.001; Fig. 3A) and the invasiveness of the A431 cells after 24 h of culture (Fig. 3B). The most effective concentration was 0.5 µg/ml (P=0.002).

View Article: PubMed Central - PubMed

ABSTRACT

The antimicrobial peptide LL-37 not only contributes to the host defence against microbial invasion but also regulates immune activity, angiogenesis and cell proliferation. Studies have shown that LL-37 participates in the development of a variety of tumours, such as lung cancer, ovarian cancer, breast cancer and melanoma. However, the role of LL-37 in the development of skin squamous cell carcinoma (SCC) is not clear. The present study used immunohistochemistry to confirm that the expression of human DNA-binding protein A (dbpA) was increased in SCC tissues. After stimulating SCC A341 cells, LL-37 was shown promote the proliferation, migration and invasion of these malignant cells. LL-37 also promoted the upregulation of dbpA mRNA and protein expression. In addition, after using small interfering RNA to silence the normal dbpA expression in these malignant cells, the proliferation and invasion of the tumor cells were significantly reduced. When the NF-&kappa;B inhibitor PDTC was used to inhibit the process of LL-37-stimulated cells, it was found that the original upregulated expression of dbpA was downregulated. Overall, the present demonstrated that by upregulating the expression of dbpA, LL-37 can promote the proliferation and invasion of tumour cells, and that this process depends on the NF-&kappa;B signalling pathway.

No MeSH data available.


Related in: MedlinePlus