Novel Function for Vascular Endothelial Growth Factor Receptor-1 on Epidermal Keratinocytes

Wilgus, Traci A.; Matthies, Annette M.; Radek, Katherine A.; Dovi, Julia V.; Burns, Aime L.; Shankar, Ravi; DiPietro, Luisa A.

doi:10.1016/s0002-9440(10)61213-8

Cited by 118 publications

(115 citation statements)

References 48 publications

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“…VEGFR-1 and -2 induce KC proliferation and migration and decrease cell adhesion on VEGF-A binding. 67,68 Therefore, VEGF-A functions as an autocrine mitogenic and motogenic growth factor for KCs, and as a paracrine growth factor for angiogenesis and granulation tissue formation.…”

Section: 32mentioning

confidence: 99%

The Roles of Growth Factors in Keratinocyte Migration

Seeger

Paller

2015

Advances in Wound Care

163

126

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Section: 32mentioning

confidence: 99%

The Roles of Growth Factors in Keratinocyte Migration

Seeger

Paller

2015

Advances in Wound Care

163

126

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“…Several experiments have shown the presence of a paracrine feedback loop (46)(47)(48), established through VEGF, between keratinocytes and endothelial cells. Furthermore, stromal secretion of PDGF from cell-matrix fibroblasts may also be important in the biology of skin dermis (49).…”

Section: Cell Signaling and Skin Toxicitymentioning

confidence: 99%

New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

Aparicio-Gallego

Blanco

Figueroa

et al. 2011

Molecular Cancer Therapeutics

104

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The introduction of targeted therapy represents a major advance in the treatment of tumor progression. Targeted agents are a novel therapeutic approach developed to disrupt different cellular signaling pathways. The tyrosine kinase inhibitor sunitinib specifically blocks multiple tyrosine kinase receptors that are involved in the progression of many tumors. Sunitinib is the current standard of care in first-line treatment of advanced renal cell carcinoma, and it is approved in imatinib-intolerant and imatinib-refractory gastrointestinal stromal tumors. However, it is increasingly evident that sunitinib may display collateral effects on other proteins beyond its main target receptors, eliciting undesirable and unexpected adverse events. A better understanding of the molecular mechanisms underlying these undesirable sunitinib-associated side effects will help physicians to maximize efficacy of sunitinib and minimize adverse events. Here, we focus on new insights into molecular mechanisms that may mediate sunitinib-associated adverse events. Mol Cancer Ther; 10(12); 2215-23. Ó2011 AACR.

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“…In this study, we systematically screened the expression of VEGF receptors and coreceptors in the epidermis. While this work was going on, Wilgus et al (18) reported that VEGFR-1, but not VEGFR-2, was detected in murine keratinocytes during wound repair and in normal human epidermal keratinocytes. Based on other functional assays, they claimed a novel role of VEGF and VEGFR-1 interaction in keratinocytes during wound healing (18).…”

Section: Introductionmentioning

confidence: 99%

“…While this work was going on, Wilgus et al (18) reported that VEGFR-1, but not VEGFR-2, was detected in murine keratinocytes during wound repair and in normal human epidermal keratinocytes. Based on other functional assays, they claimed a novel role of VEGF and VEGFR-1 interaction in keratinocytes during wound healing (18). Most recently, the expression of NRP-1 was also characterized in keratinocytes in vitro and in vivo (19).…”

Section: Introductionmentioning

confidence: 99%

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Immunolocalization and Expression of Vascular Endothelial Growth Factor Receptors (VEGFRs) and Neuropilins (NRPs) on Keratinocytes in Human Epidermis

Man

Yang

Cai

et al. 2006

Mol Med

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Vascular endothelial growth factor (VEGF) plays an important role in normal and pathological angiogenesis. VEGF receptors (VEGFRs, including VEGFR-1, VEGFR-2, and VEGFR-3) and neuropilins (NRPs, including NRP-1 and NRP-2) are high-affinity receptors for VEGF and are typically considered to be specific for endothelial cells. Here we showed expression of VEGFRs and NRPs on cultured epidermal keratinocytes at both mRNA and protein levels. We further localized these receptors by immunofluorescence (IF) staining in the epidermis of surgical skin specimens. We found positive staining for VEGFRs and NRPs in all layers of the epidermis except for the stratum corneum. VEGFR-1 and VEGFR-2 are primarily expressed on the cytoplasmic membrane of basal cells and the adjacent spinosum keratinocytes. All layers of the epidermis except for the horny cell layer demonstrated a uniform pattern of VEGFR-3, NRP-1, and NRP-2. Sections staining for NRP-1 and NRP-2 also showed diffuse intense fluorescence and were localized to the cell membrane and cytoplasm of keratinocytes. In another panel of experiments, keratinocytes were treated with different concentrations of VEGF, with or without VEGFR-2 neutralizing antibody in culture. VEGF enhanced the proliferation and migration of keratinocytes, and these effects were partially inhibited by pretreatment with VEGFR-2 neutralizing antibody. Adhesion of keratinocytes to type IV collagen-coated culture plates was decreased by VEGF treatment, but this reduction could be completely reversed by pretreatment with VEGFR-2 neutralizing antibody. Taken together, our results suggest that the expression of VEGFRs and NRPs on keratinocytes may constitute important regulators for its activity and may possibly be responsible for the autocrine signaling in the epidermis.

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Novel Function for Vascular Endothelial Growth Factor Receptor-1 on Epidermal Keratinocytes

Cited by 118 publications

References 48 publications

The Roles of Growth Factors in Keratinocyte Migration

The Roles of Growth Factors in Keratinocyte Migration

New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

Immunolocalization and Expression of Vascular Endothelial Growth Factor Receptors (VEGFRs) and Neuropilins (NRPs) on Keratinocytes in Human Epidermis

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