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In vitro retinoid-induced growth inhibition and morphologic differentiation of canine osteosarcoma cells

Sung-Hyeok Hong DVM, MS1, Tsuyoshi Kadosawa DVM, PhD2, Kazutoshi Nozaki DVM, PhD3, Manabu Mochizuki DVM, PhD4, Satoru Matsunaga DVM5, Ryohei Nishimura DVM, PhD6, and Nobuo Sasaki DVM, PhD7
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  • 1 Laboratory of Veterinary Surgery, Division of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan 113-8657.
  • | 2 Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan 060-0818.
  • | 3 Laboratory of Veterinary Surgery, Division of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan 113-8657.
  • | 4 Laboratory of Veterinary Surgery, Division of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan 113-8657.
  • | 5 Veterinary Medical Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan 113-8657.
  • | 6 Laboratory of Veterinary Surgery, Division of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan 113-8657.
  • | 7 Laboratory of Veterinary Surgery, Division of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan 113-8657.

Abstract

Objective—To determine differentiation and growth inhibition effects of retinoids on canine osteosarcoma cells.

Sample Population—3 osteosarcoma cell lines established from osteosarcomas in dogs.

Procedure—Osteosarcoma cells were incubated with various concentrations of all-trans-retinoic acid and 9-cis-retinoic acid or control medium, counted daily for 10 days, and evaluated for morphologic changes. Synthesis of DNA was measured by use of a cell proliferation ELISA. To analyze effect of retinoids on colony formation on plastic dishes, cells were cultured for 14 days, fixed, and stained; number of colonies was counted.

Results—In a dose-dependent manner, both retinoids induced morphologic differentiation and growth inhibition in the 3 osteosarcoma cell lines and inhibited each cell's ability to form anchorage-dependent colonies.

Conclusion and Clinical Relevance—Retinoids induced differentiation of osteosarcoma cells of dogs, resulting in altered expression of their malignant phenotype. Induction of differentiation by retinoids may have potential as an adjunctive treatment for osteosarcoma in dogs. (Am J Vet Res 2000;61:69–73)

Abstract

Objective—To determine differentiation and growth inhibition effects of retinoids on canine osteosarcoma cells.

Sample Population—3 osteosarcoma cell lines established from osteosarcomas in dogs.

Procedure—Osteosarcoma cells were incubated with various concentrations of all-trans-retinoic acid and 9-cis-retinoic acid or control medium, counted daily for 10 days, and evaluated for morphologic changes. Synthesis of DNA was measured by use of a cell proliferation ELISA. To analyze effect of retinoids on colony formation on plastic dishes, cells were cultured for 14 days, fixed, and stained; number of colonies was counted.

Results—In a dose-dependent manner, both retinoids induced morphologic differentiation and growth inhibition in the 3 osteosarcoma cell lines and inhibited each cell's ability to form anchorage-dependent colonies.

Conclusion and Clinical Relevance—Retinoids induced differentiation of osteosarcoma cells of dogs, resulting in altered expression of their malignant phenotype. Induction of differentiation by retinoids may have potential as an adjunctive treatment for osteosarcoma in dogs. (Am J Vet Res 2000;61:69–73)