The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035 suppresses expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro

George W. Cole, Annette M. Alleva, Rishindra M. Reddy, Justin B. Maxhimer, JingTong Zuo, David S. Schrump, Dao Nguyen

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: Malignant pleural mesothelioma is notoriously refractory to aggressive multimodality therapy. Epidermal growth factor receptor expression has been observed on malignant pleural mesothelioma cells. Epidermal growth factor receptor-mediated signaling promotes tumorigenesis and metastasis of cancer cells. The purpose of this study is to evaluate the ability of the epidermal growth factor receptor tyrosine kinase inhibitor PD153035 to abrogate the expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro. Methods: Epidermal growth factor receptor expression of malignant pleural mesothelioma cells and primary normal cells was quantitated by means of flow cytometry. PD153035-mediated growth inhibition was determined by means of 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan and clonogenic assays. Cell motility and invasion of extracellular matrix was evaluated with in vitro wound-healing and Matrigel invasion assays, respectively. Vascular epidermal growth factor levels in conditioned media were measured by using enzyme-linked immunosorbent assay. Results: Epidermal growth factor receptor expression was detected on all 6 cultured malignant pleural mesothelioma cells, with 4 of 6 having normal receptor expression and 2 of 6 overexpressing the receptor. PD153035 suppressed cell motility and cell invasion through a Matrigel membrane, regardless of the baseline epidermal growth factor receptor expression. Decreased vascular epidermal growth factor production and significant inhibition of growth only occurred in malignant pleural mesothelioma cells that overexpress epidermal growth factor receptor. Conclusions: Epidermal growth factor receptor tyrosine kinase inhibitor PD153035 significantly inhibited motility and invasion in malignant pleural mesothelioma cells in vitro, regardless of their epidermal growth factor receptor expression levels. Inhibition of epidermal growth factor receptor-dependent signaling might be a useful strategy to diminish malignant pleural mesothelioma recurrence after aggressive cytoreductive surgery.

Original languageEnglish
Pages (from-to)1010-1017
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume129
Issue number5
DOIs
StatePublished - May 1 2005
Externally publishedYes

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Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Phenotype
Epidermal Growth Factor
Cell Movement
Blood Vessels
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline
In Vitro Techniques
Malignant Mesothelioma
Conditioned Culture Medium
Growth
Wound Healing
Extracellular Matrix
Flow Cytometry
Carcinogenesis
Enzyme-Linked Immunosorbent Assay
Neoplasm Metastasis
Recurrence
Membranes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035 suppresses expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro. / Cole, George W.; Alleva, Annette M.; Reddy, Rishindra M.; Maxhimer, Justin B.; Zuo, JingTong; Schrump, David S.; Nguyen, Dao.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 129, No. 5, 01.05.2005, p. 1010-1017.

Research output: Contribution to journalArticle

Cole, George W. ; Alleva, Annette M. ; Reddy, Rishindra M. ; Maxhimer, Justin B. ; Zuo, JingTong ; Schrump, David S. ; Nguyen, Dao. / The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035 suppresses expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro. In: Journal of Thoracic and Cardiovascular Surgery. 2005 ; Vol. 129, No. 5. pp. 1010-1017.
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AU - Reddy, Rishindra M.

AU - Maxhimer, Justin B.

AU - Zuo, JingTong

AU - Schrump, David S.

AU - Nguyen, Dao

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