A Potential Oncogenic Activity of Platelet-Derived Growth Factor D in Prostate Cancer Progression

Ustach, Carolyn V.; Taube, Marcus E.; Hurst, Newton J.; Bhagat, Sunita; Bonfil, R. Daniel; Cher, Michael L.; Schuger, Lucia; Kim, Hyeong Reh Choi

doi:10.1158/0008-5472.can-03-3047

Cited by 87 publications

(109 citation statements)

References 33 publications

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“…It has been reported that PDGF-D signaling is frequently deregulated in human malignancies with up-regulated expression of PDGF-D in lung, prostate, renal, ovarian, and brain cancer (3,(9)(10)(11)(12)(13). These results suggest that PDGF-D plays important roles in the oncogenesis of several malignancies.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-κB Signaling

et al. 2007

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Section: Introductionmentioning

confidence: 99%

Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-κB Signaling

et al. 2007

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“…Similar to PDGF-B, PDGF-D is important for cellular transformation and support of tumor development, probably due to exclusive or preferential signaling through PDGFR␤ (8,30). A similar function has been ascribed to the PDGFR␣ agonist PDGF-C (5,6).…”

Section: Discussionmentioning

confidence: 93%

Expression of platelet‐derived growth factors C and D in the synovial membrane of patients with rheumatoid arthritis and osteoarthritis

Pohlers

Huber

Ukena

et al. 2006

Arthritis & Rheumatism

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“…In human cancers, PDGFD up-regulation has been documented for prostate, lung, renal, ovarian, brain, breast, and pancreatic cancers (31,32). However, the mechanisms underlying the effect of PDGF-DD on tumor growth are still largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD

Cortez

Gladh

Braun

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, plateletderived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development.However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.tumor heterogeneity | platelet-derived growth factor-DD | neuroendocrine tumor

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A Potential Oncogenic Activity of Platelet-Derived Growth Factor D in Prostate Cancer Progression

Abstract: ABSTRACT

Cited by 87 publications

References 33 publications

Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-κB Signaling

Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-κB Signaling

Expression of platelet‐derived growth factors C and D in the synovial membrane of patients with rheumatoid arthritis and osteoarthritis

Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD

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