Platelet-Derived Growth Factor B-Chain of Hematopoietic Origin Is Not Necessary for Granulation Tissue Formation and Its Absence Enhances Vascularization

Buetow, Bernard S.; Crosby, Jeff; Kaminski, Wolfgang E.; Ramachandran, Ravi K.; Lindahl, Per; Martin, Paul J.; Betsholtz, Christer; Seifert, Ronald A.; Raines, Elaine W.; Bowen‐Pope, Daniel F.

doi:10.1016/s0002-9440(10)63033-7

Cited by 20 publications

(11 citation statements)

References 38 publications

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“…Disabling the local chemotactic gradient of PDGF-BB has been shown to reduce vascularization. 24 Therefore, we engineered the implanted endothelial cells to overexpress PDGF-BB to establish a local chemotactic gradient of PDGF-BB that is critical for pericyte recruitment in nascent vessels. 25 However, unexpectedly, we found a contextual effect of perivascular cell precursors in this system.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical Effects of PDGF-BB Overexpression in Endothelial Cells on Engineered Blood Vessels In Vivo

Tam

Duda

et al. 2009

The American Journal of Pathology

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Section: Discussionmentioning

confidence: 99%

Paradoxical Effects of PDGF-BB Overexpression in Endothelial Cells on Engineered Blood Vessels In Vivo

Tam

Duda

et al. 2009

The American Journal of Pathology

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“…13 This result suggests a redundancy of PDGF-B-like growth factors. PDGF-D could perhaps provide a redundant function because it also binds to and activates one of the receptors for PDGF-B.…”

Section: Introductionmentioning

confidence: 90%

PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis

Uutela

Wirzenius

Paavonen

et al. 2004

Blood

154

116

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Platelet-derived growth factor-D (PDGF-D IntroductionPlatelet-derived growth factor (PDGF) is a mitogen for various cell types, including fibroblasts and smooth muscle cells. Although originally purified from human platelets, 1 current data indicate that several different cell types can produce PDGF in vitro and in vivo. 2 Until recently, the PDGF family of growth factors was composed of PDGF-A and PDGF-B chain homodimers and heterodimers. Recently, however, 2 novel homologous genes were isolated, PDGF-C 3 and PDGF-D. 4-6 PDGF-C and PDGF-D form disulfide-bonded homodimers, but they do not appear to heterodimerize with PDGF-A or PDGF-B chains, and they differ from the latter by having an N-terminal CUB-domain that is proteolytically cleaved before receptor binding. [3][4][5] PDGFs bind to and activate 2 structurally related protein tyrosine kinase receptors, PDGF receptor-␣ and PDGF receptor-␤. According to published data, the ␣-receptor binds PDGF-AA, PDGF-BB, PDGF-AB, and PDGF-CC, whereas the ␤-receptor binds PDGF-BB and PDGF-DD. [2][3][4] Although the exact biologic functions of PDGF-D are unknown, it has been shown to stimulate tumor growth and angiogenesis, 7-9 and it is implicated in glomerulonephritis. 10 Considerable interest focuses on the potential role of PDGF-D in wound healing. Reepithelialization, extracellular matrix deposition, and angiogenesis are all part of the wound healing process, and PDGFs are involved in various stages of this process (for a review, see Martin 11 ).Although most of the PDGF-B in wounds is produced by cells of hematopoietic origin, 12 wound healing occurs normally in mice that undergo transplantation with bone marrow derived from pdgfb null mice. 13 This result suggests a redundancy of PDGF-B-like growth factors. PDGF-D could perhaps provide a redundant function because it also binds to and activates one of the receptors for PDGF-B.Here we have addressed the effects of PDGF-D overexpression in normal skin and muscle and its effects on wound healing. We overexpressed the human PDGF-D cDNA under the keratin 14 (K14) promoter in the basal skin keratinocytes of transgenic mice. Because this promoter is strongly up-regulated during the woundhealing process, abundant PDGF-D is delivered to the wounds. 14 Furthermore, we cloned full-length PDGF-D and the activated growth factor domain into an adeno-associated virus (AAV) vector, overexpressed it alone or in combination with a known angiogenic factor, vascular endothelial growth factor-E (VEGF-E), and examined its effects on the generated blood vessels. Materials and methods Generation and analysis of K14-PDGF-D transgenic miceHuman PDGF-D cDNA (base pair [bp] 176-1285; GenBank sequence number AF336376) was inserted into the BamHI site of the K14 promoter expression vector 15 ( Figure 1A). The resultant construct was digested with EcoRI and SphI, and the expression cassette was purified. A 5-ng/mL For personal use only. on June 19, 2019. by guest www.bloodjournal.org From solution of the DNA was injected into fertilized eggs of t...

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“…This results in proliferation and migration of pericytes/VSM cells during maturation of vessels (Betsholtz, 2004;Hoch and Soriano, 2003). Studies show depletion of pdgfb specifically in the endothelium, results in significant pericyte deficiency in the vasculature (Bjarnegard et al, 2004;Enge et al, 2002) whilst similar depletion of pdgfb in hematopoetic or neuronal cells had no effect on the vasculature (Buetow et al, 2001;Enge et al, 2003). These interactions highlight the critical role of endothelium-derived PDGF in pericyte recruitment.…”

Section: Pericyte/vsm-endothelial Cell Interactions In the Tumor Micrmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

687

327

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High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

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Platelet-Derived Growth Factor B-Chain of Hematopoietic Origin Is Not Necessary for Granulation Tissue Formation and Its Absence Enhances Vascularization

Cited by 20 publications

References 38 publications

Paradoxical Effects of PDGF-BB Overexpression in Endothelial Cells on Engineered Blood Vessels In Vivo

Paradoxical Effects of PDGF-BB Overexpression in Endothelial Cells on Engineered Blood Vessels In Vivo

PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis

The brain tumor microenvironment

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