BACKGROUND: In tumor angiogenesis there is a complex interplay between endothelial, stromal, and tumor cells (neoplastic epithelial cells). Platelet-derived growth factors (PDGFs) and receptors (PDGFRs) are pivotal in this interaction, and important targets in novel antiangiogenic therapies. This study investigates the prognostic impact of these molecular markers in tumor cells and tumor stroma of resected non-small cell lung cancer (NSCLC) tumors. METHODS: Tumor tissue samples from 335 resected patients with stage I to IIIA NSCLC were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers PDGF-A, -B, -C, and -D and PDGFR-alpha and -beta. RESULTS: In univariate analyses, high tumor cell expression of PDGF-B (p = 0.001), PDGF-C (p = 0.01), and PDGFR-alpha (p = 0.026) were negative prognostic indicators for disease-specific survival. In tumor stroma, high expression of PDGF-A (p = 0.009), PDGF-B (p = 0.04), PDGF-D (p = 0.019), and PDGFR-alpha (p = 0.019) correlated with good prognosis. In multivariate analyses, high tumor cell PDGF-B (p = 0.001) and PDGFR-alpha (p = 0.047) expression were independent negative prognostic factors for disease-specific survival, whereas in stromal cells high PDGF-A (p = 0.001) expression had an independent positive survival impact. CONCLUSION: Our results indicate PDGF-B and PDGFR-alpha inhibition as an interesting approach in NSCLC treatment, but also demonstrates the importance of understanding the cellular crosstalk between endothelial, stromal, and tumor cells when targeting PDGF markers.
BACKGROUND: In tumor angiogenesis there is a complex interplay between endothelial, stromal, and tumor cells (neoplastic epithelial cells). Platelet-derived growth factors (PDGFs) and receptors (PDGFRs) are pivotal in this interaction, and important targets in novel antiangiogenic therapies. This study investigates the prognostic impact of these molecular markers in tumor cells and tumor stroma of resected non-small cell lung cancer (NSCLC) tumors. METHODS:Tumor tissue samples from 335 resected patients with stage I to IIIA NSCLC were obtained and tissue microarrays were constructed from duplicate cores of tumor cells and tumor-related stroma from each specimen. Immunohistochemistry was used to evaluate the expression of the molecular markers PDGF-A, -B, -C, and -D and PDGFR-alpha and -beta. RESULTS: In univariate analyses, high tumor cell expression of PDGF-B (p = 0.001), PDGF-C (p = 0.01), and PDGFR-alpha (p = 0.026) were negative prognostic indicators for disease-specific survival. In tumor stroma, high expression of PDGF-A (p = 0.009), PDGF-B (p = 0.04), PDGF-D (p = 0.019), and PDGFR-alpha (p = 0.019) correlated with good prognosis. In multivariate analyses, high tumor cell PDGF-B (p = 0.001) and PDGFR-alpha (p = 0.047) expression were independent negative prognostic factors for disease-specific survival, whereas in stromal cells high PDGF-A (p = 0.001) expression had an independent positive survival impact. CONCLUSION: Our results indicate PDGF-B and PDGFR-alpha inhibition as an interesting approach in NSCLC treatment, but also demonstrates the importance of understanding the cellular crosstalk between endothelial, stromal, and tumor cells when targeting PDGF markers.
Authors: Elly Marcq; Vasiliki Siozopoulou; Jorrit De Waele; Jonas van Audenaerde; Karen Zwaenepoel; Eva Santermans; Niel Hens; Patrick Pauwels; Jan P van Meerbeeck; Evelien L J Smits Journal: Oncoimmunology Date: 2016-11-28 Impact factor: 8.110
Authors: Anne S Tsao; Wei Wei; Elisabetta Kuhn; Loreto Spencer; Luisa M Solis; Milind Suraokar; J Jack Lee; Waun Ki Hong; Ignacio I Wistuba Journal: Clin Lung Cancer Date: 2011-05-17 Impact factor: 4.785
Authors: David E Gerber; Paul Swanson; Ariel Lopez-Chavez; Lucas Wong; Afshin Dowlati; Nathan A Pennell; Damien M Cronier; Amy Qin; Robert Ilaria; Jan Cosaert; Ashwin Shahir; Maria Q Baggstrom Journal: Lung Cancer Date: 2017-07-18 Impact factor: 5.705
Authors: David E Gerber; Puja Gupta; Michael T Dellinger; Jason E Toombs; Michael Peyton; Inga Duignan; Jennifer Malaby; Timothy Bailey; Colleen Burns; Rolf A Brekken; Nick Loizos Journal: Mol Cancer Ther Date: 2012-08-28 Impact factor: 6.261