Cell surface receptor expression patterns in osteosarcoma

Sheref E. Hassan, Mikhail Bekarev, Mimi Kim, Juan Lin, Sajida Piperdi, Richard Gorlick, David S. Geller

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

BACKGROUND: Although the presence of numerous cell signaling receptors in osteosarcoma is known, their simultaneous characterization has not been performed to date. The current study sought to characterize and quantify the expression of cell surface receptors across a variety of osteosarcoma cell lines. METHODS: Standard (n = 4) and patient-derived (n = 10) osteosarcoma cell lines were cultured and labeled with antibodies to epidermal growth factor receptor, human epidermal growth factor receptor (HER)-2, HER-3, HER-4, insulin-like growth factor 1 receptor (IGF-1R), IGF-2R, insulin receptor (IR), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, c-Met, fibroblast growth factor receptor (FGFR)-2, FGFR-3, and platelet-derived growth factor receptor (PDGFR)-β. Cell surface examination was performed using flow cytometry, and the geometric fluorescent mean for each receptor was calculated and compared against a positive control. RESULTS: Significant overexpression of IGF-2R was shown in all cell lines, with an average geometric mean above the upper expression quartile. A variable expression pattern was seen for c-Met, PDGFR-β, IR, IGFR-1, HER-2, and VEGFR-3 with expression values for the remaining receptors mainly in the lower quartile. An apparent association between the expression of IGF-1R and HER-2 and between the expression of PDGFR-β and IR was demonstrated. CONCLUSION: IGF-2R was consistently overexpressed on the cell surface across all tested osteosarcoma cell lines. Substantial, although variable, expression of c-Met, HER-2, IGF-1R, VEGFR-3, IR, and PDGFR-β was demonstrated as well, suggesting that these receptors may contribute to osteosarcoma aggressiveness and biological heterogeneity and may serve as potential targets within a subset of tumors. Associated receptor expression may provide new insight into common regulatory factors or pathways. Targeting either common factors or targeting multiple specific receptors may have therapeutic relevance.

Original languageEnglish (US)
Pages (from-to)740-749
Number of pages10
JournalCancer
Volume118
Issue number3
DOIs
StatePublished - Feb 1 2012

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Cell Surface Receptors
Osteosarcoma
Platelet-Derived Growth Factor Receptors
Insulin Receptor
Vascular Endothelial Growth Factor Receptor-3
Somatomedin Receptors
Cell Line
Receptor, Fibroblast Growth Factor, Type 3
Receptor, Fibroblast Growth Factor, Type 2
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Insulin-Like Growth Factor I
Epidermal Growth Factor Receptor
Flow Cytometry
Antibodies
Neoplasms

Keywords

  • flow cytometry
  • IGF-2R
  • osteosarcoma
  • surface receptors
  • targeted therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cell surface receptor expression patterns in osteosarcoma. / Hassan, Sheref E.; Bekarev, Mikhail; Kim, Mimi; Lin, Juan; Piperdi, Sajida; Gorlick, Richard; Geller, David S.

In: Cancer, Vol. 118, No. 3, 01.02.2012, p. 740-749.

Research output: Contribution to journalArticle

Hassan, SE, Bekarev, M, Kim, M, Lin, J, Piperdi, S, Gorlick, R & Geller, DS 2012, 'Cell surface receptor expression patterns in osteosarcoma', Cancer, vol. 118, no. 3, pp. 740-749. https://doi.org/10.1002/cncr.26339
Hassan SE, Bekarev M, Kim M, Lin J, Piperdi S, Gorlick R et al. Cell surface receptor expression patterns in osteosarcoma. Cancer. 2012 Feb 1;118(3):740-749. https://doi.org/10.1002/cncr.26339
Hassan, Sheref E. ; Bekarev, Mikhail ; Kim, Mimi ; Lin, Juan ; Piperdi, Sajida ; Gorlick, Richard ; Geller, David S. / Cell surface receptor expression patterns in osteosarcoma. In: Cancer. 2012 ; Vol. 118, No. 3. pp. 740-749.
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AB - BACKGROUND: Although the presence of numerous cell signaling receptors in osteosarcoma is known, their simultaneous characterization has not been performed to date. The current study sought to characterize and quantify the expression of cell surface receptors across a variety of osteosarcoma cell lines. METHODS: Standard (n = 4) and patient-derived (n = 10) osteosarcoma cell lines were cultured and labeled with antibodies to epidermal growth factor receptor, human epidermal growth factor receptor (HER)-2, HER-3, HER-4, insulin-like growth factor 1 receptor (IGF-1R), IGF-2R, insulin receptor (IR), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, c-Met, fibroblast growth factor receptor (FGFR)-2, FGFR-3, and platelet-derived growth factor receptor (PDGFR)-β. Cell surface examination was performed using flow cytometry, and the geometric fluorescent mean for each receptor was calculated and compared against a positive control. RESULTS: Significant overexpression of IGF-2R was shown in all cell lines, with an average geometric mean above the upper expression quartile. A variable expression pattern was seen for c-Met, PDGFR-β, IR, IGFR-1, HER-2, and VEGFR-3 with expression values for the remaining receptors mainly in the lower quartile. An apparent association between the expression of IGF-1R and HER-2 and between the expression of PDGFR-β and IR was demonstrated. CONCLUSION: IGF-2R was consistently overexpressed on the cell surface across all tested osteosarcoma cell lines. Substantial, although variable, expression of c-Met, HER-2, IGF-1R, VEGFR-3, IR, and PDGFR-β was demonstrated as well, suggesting that these receptors may contribute to osteosarcoma aggressiveness and biological heterogeneity and may serve as potential targets within a subset of tumors. Associated receptor expression may provide new insight into common regulatory factors or pathways. Targeting either common factors or targeting multiple specific receptors may have therapeutic relevance.

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