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Dasatinib Modulates Invasive and Migratory Properties of Canine Osteosarcoma and has Therapeutic Potential in Affected Dogs.

Marley K, Gullaba J, Seguin B, Gelberg HB, Helfand SC - Transl Oncol (2015)

Bottom Line: HGF induces secretion of different forms of MMP in different cell lines.The HGF-driven increase in viability and metastatic behaviors we observed are more uniformly inhibited by dasatinib.These observations suggest a potential clinical benefit of adjuvant dasatinib treatment for dogs with OS.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences Oregon State University, 105 Magruder Hall, Corvallis OR, 97331, USA. Electronic address: kevin.marley@oregonstate.edu.

No MeSH data available.


Related in: MedlinePlus

Migration assay. (A) HGF increased migration in both cell lines, but the TKIs crizotinib and dasatinib were able to suppress migration only in the COS cell line. *P ≤ .05. Data are representative of three independent experiments. (B) Representative photomicrographs of cells treated with HGF ± TKIs. After 24 hours, cells that migrated into the box overlay were counted (data shown in A).
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f0005: Migration assay. (A) HGF increased migration in both cell lines, but the TKIs crizotinib and dasatinib were able to suppress migration only in the COS cell line. *P ≤ .05. Data are representative of three independent experiments. (B) Representative photomicrographs of cells treated with HGF ± TKIs. After 24 hours, cells that migrated into the box overlay were counted (data shown in A).

Mentions: HGF caused an increase in migration in serum-starved canine OS cells (P ≤ .05, Figure 1), and low-concentration (20 nM) TKI incubation suppressed migration in COS but not Clone-4 cells. The increase in migration attributed to HGF was significant in both cell lines, but the rate of migration of the Clone-4 cells was much lower (Figure 1). HGF-induced invasion was more consistent and was more than 100% greater than controls in both cell lines (P < .05, Figure 2). The TKIs' ability to prevent this increase was specific only to dasatinib. In fact, dasatinib not only prevented the HGF-induced increase but reduced overall invasion from 205 to 25% of that seen in the serum-starved and untreated cells (Figure 2).


Dasatinib Modulates Invasive and Migratory Properties of Canine Osteosarcoma and has Therapeutic Potential in Affected Dogs.

Marley K, Gullaba J, Seguin B, Gelberg HB, Helfand SC - Transl Oncol (2015)

Migration assay. (A) HGF increased migration in both cell lines, but the TKIs crizotinib and dasatinib were able to suppress migration only in the COS cell line. *P ≤ .05. Data are representative of three independent experiments. (B) Representative photomicrographs of cells treated with HGF ± TKIs. After 24 hours, cells that migrated into the box overlay were counted (data shown in A).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4562978&req=5

f0005: Migration assay. (A) HGF increased migration in both cell lines, but the TKIs crizotinib and dasatinib were able to suppress migration only in the COS cell line. *P ≤ .05. Data are representative of three independent experiments. (B) Representative photomicrographs of cells treated with HGF ± TKIs. After 24 hours, cells that migrated into the box overlay were counted (data shown in A).
Mentions: HGF caused an increase in migration in serum-starved canine OS cells (P ≤ .05, Figure 1), and low-concentration (20 nM) TKI incubation suppressed migration in COS but not Clone-4 cells. The increase in migration attributed to HGF was significant in both cell lines, but the rate of migration of the Clone-4 cells was much lower (Figure 1). HGF-induced invasion was more consistent and was more than 100% greater than controls in both cell lines (P < .05, Figure 2). The TKIs' ability to prevent this increase was specific only to dasatinib. In fact, dasatinib not only prevented the HGF-induced increase but reduced overall invasion from 205 to 25% of that seen in the serum-starved and untreated cells (Figure 2).

Bottom Line: HGF induces secretion of different forms of MMP in different cell lines.The HGF-driven increase in viability and metastatic behaviors we observed are more uniformly inhibited by dasatinib.These observations suggest a potential clinical benefit of adjuvant dasatinib treatment for dogs with OS.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences Oregon State University, 105 Magruder Hall, Corvallis OR, 97331, USA. Electronic address: kevin.marley@oregonstate.edu.

No MeSH data available.


Related in: MedlinePlus