Disintegrin targeting of an αvβ3 integrin-over-expressing high-metastatic human osteosarcoma with echistatin inhibits cell proliferation, migration, invasion and adhesion in vitro

The in vitro efficacy of the disintegrin echistatin was tested on a high-metastatic variant of 143B human osteosarcoma, 143B-LM4, which over-expresses αvβ3 integrin. Echistatin is an RGD cyclic peptide and an antagonist of αvβ3 integrin. In the present study, echistatin inhibited cell proliferation, migration, invasion, and adhesion of 143B-LM4 cells. 143B-LM4 cell proliferation decreased after treatment with echistatin in a time-dependent and dose-dependent manner (P <0.01). In vitro migration and invasion of 143B-LM4 cells were also inhibited by echistatin in a dose-dependent manner (P <0.01, respectively). Cell adhesion to vitronectin of 143B-LM4 cells was also inhibited by echistatin in a dose-dependent manner (P <0.01). These results suggest that αvβ3 integrin may be an effective target for osteosarcoma.

[1]  N. Sugimoto,et al.  High lung-metastatic variant of human osteosarcoma cells, selected by passage of lung metastasis in nude mice, is associated with increased expression of α(v)β(3) integrin. , 2013, Anticancer research.

[2]  H. Tsuchiya,et al.  Imaging the inhibition by anti‐β1 integrin antibody of lung seeding of single osteosarcoma cells in live mice , 2012, International journal of cancer.

[3]  Karsten König,et al.  The bulge area is the origin of nestin‐expressing pluripotent stem cells of the hair follicle , 2011, Journal of cellular biochemistry.

[4]  M. van Glabbeke,et al.  Survival after recurrent osteosarcoma: data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials. , 2011, European journal of cancer.

[5]  Fengzhi Li,et al.  Exploring long-term protection of normal human fibroblasts and epithelial cells from chemotherapy in cell culture , 2011, Oncotarget.

[6]  H. Tsuchiya,et al.  Caffeine-potentiated chemotherapy for metastatic osteosarcoma , 2009, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[7]  B. Crompton,et al.  Survival after recurrence of osteosarcoma: A 20‐year experience at a single institution , 2006, Pediatric blood & cancer.

[8]  E. Novellino,et al.  Novel and Selective αvβ3 Receptor Peptide Antagonist: Design, Synthesis, and Biological Behavior , 2006 .

[9]  M. Blagosklonny Target for cancer therapy: proliferating cells or stem cells , 2006, Leukemia.

[10]  H. Hosalkar,et al.  Endoprosthetic Reconstructions: Results of Long-term Followup of 139 Patients , 2005, Clinical orthopaedics and related research.

[11]  N. Yamamoto,et al.  Reconstruction using an autograft containing tumour treated by liquid nitrogen. , 2005, The Journal of bone and joint surgery. British volume.

[12]  A. Huvos,et al.  The patterns of relapse in osteosarcoma: The memorial Sloan‐Kettering experience , 2004, Pediatric blood & cancer.

[13]  M. Blagosklonny Matching targets for selective cancer therapy. , 2003, Drug discovery today.

[14]  M. Blagosklonny Tissue-selective therapy of cancer , 2003, British Journal of Cancer.

[15]  M. Blagosklonny Treatment with inhibitors of caspases, that are substrates of drug transporters, selectively permits chemotherapy-induced apoptosis in multidrug-resistant cells but protects normal cells , 2001, Leukemia.

[16]  S. Ferrari,et al.  Osteosarcoma of the extremities with synchronous lung metastases: long-term results in 44 patients treated with neoadjuvant chemotherapy. , 1998, Journal of chemotherapy.

[17]  K. Devaney Dahlin's Bone Tumors. General Aspects and Data on 11,087 Cases , 1996 .

[18]  K. Unni,et al.  Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases , 1996 .

[19]  S. Ferrari,et al.  Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin , 1993, Cancer.

[20]  A. Huvos,et al.  Osteogenic sarcoma with clinically detectable metastasis at initial presentation. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  A. Freemont Bone Tumors. Diagnosis, Treatment, and Prognosis , 1991 .

[22]  E. Novellino,et al.  Novel and selective alpha(v)beta3 receptor peptide antagonist: design, synthesis, and biological behavior. , 2006, Journal of medicinal chemistry.

[23]  N. Yamamoto,et al.  Caffeine-assisted chemotherapy and minimized tumor excision for nonmetastatic osteosarcoma. , 1998, Anticancer research.