Prognostic significance of stromal platelet-derived growth factor beta-receptor expression in human breast cancer.
Janna Paulsson,Tobias Sjöblom,Patrick Micke,Fredrik Pontén,Göran Landberg,Carl-Henrik Heldin,Jonas Bergh,Donal J. Brennan,Karin Jirström,Arne Östman +9 more
TLDR
The prognostic significance of stromal PDGF beta-receptor expression was particularly prominent in tumors from premenopausal women and should be considered in ongoing clinical development of PDGF receptor inhibitors.Abstract:
This study systematically analyzes platelet-derived growth factor (PDGF) receptor expression in six types of common tumors as well as examines associations between PDGF β-receptor status and clinicopathological characteristics in breast cancer. PDGF receptor expression was determined by immunohistochemistry on tumor tissue microarrays. Breast tumor data were combined with prognostic factors and related to outcome endpoints. PDGF α- and β-receptors were independently expressed, at variable frequencies, in the tumor stroma of all tested tumor types. There was a significant association between PDGF β-receptor expression on fibroblasts and perivascular cells in individual colon and prostate tumors. In breast cancer, high stromal PDGF β-receptor expression was significantly associated with high histopathological grade, estrogen receptor negativity, and high HER2 expression. High stromal PDGF β-receptor expression was correlated with significantly shorter recurrence-free and breast cancer-specific survival. The prognostic significance of stromal PDGF β-receptor expression was particularly prominent in tumors from premenopausal women. Stromal PDGF α- and β-receptor expression is a common, but variable and independent, property of solid tumors. In breast cancer, stromal PDGF β-receptor expression significantly correlates with less favorable clinicopathological parameters and shorter survival. These findings highlight the prognostic significance of stromal markers and should be considered in ongoing clinical development of PDGF receptor inhibitors.read more
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Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy
David G. DeNardo,David G. DeNardo,Donal J. Brennan,Elton Rexhepaj,Brian Ruffell,Stephen L. Shiao,Stephen F. Madden,William M. Gallagher,Nikhil Wadhwani,Scott D. Keil,Sharfaa A. Junaid,Hope S. Rugo,E. Shelley Hwang,Karin Jirström,Brian L. West,Lisa M. Coussens +15 more
TL;DR: Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8+ T-cell-dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy.
Journal ArticleDOI
Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression
Mina J. Bissell,William C. Hines +1 more
TL;DR: How normal tissue homeostasis and architecture inhibit progression of cancer and how changes in the microenvironment can shift the balance of these signals to the procancerous state are reviewed.
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Hallmarks of cancer: interactions with the tumor stroma.
Kristian Pietras,Arne Östman +1 more
TL;DR: The current understanding of tumor cell interactions with the tumor stroma is reviewed with a particular focus on cancer-associated fibroblasts and pericytes.
Journal ArticleDOI
Recent developments in myofibroblast biology: paradigms for connective tissue remodeling.
Boris Hinz,Sem H. Phan,Victor J. Thannickal,Marco Prunotto,Alexis Desmoulière,John Varga,Olivier De Wever,Marc Mareel,Giulio Gabbiani +8 more
TL;DR: The origin and the specific features of the myofibroblast in diverse fibrotic lesions, such as systemic sclerosis; kidney, liver, and lung fibrosis; and the stromal reaction to certain epithelial tumors are reviewed.
Journal ArticleDOI
Activation of fibroblasts in cancer stroma.
Kati Räsänen,Antti Vaheri +1 more
TL;DR: This review focuses mainly on carcinomas and discusses the recent findings regarding the role of activated fibroblasts in driving tumor progression.
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Mina J. Bissell,Derek C. Radisky +1 more
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A Tyrosine Kinase Created by Fusion of the PDGFRA and FIP1L1 Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome
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