Cultured retinal pericytes stimulate in vitro angiogenesis of endothelial cells through secretion of a fibroblast growth factor-like molecule

Watanabe, Shiro; Morisaki, Naho; Tezuka, Mariko; Fukuda, Kuniaki; Ueda, Shirou; Koyama, Noriyuki; Yokote, Koutaro; Kanzaki, Tetsuto; Yoshida, Sho; Saitō, Yasushi

doi:10.1016/s0021-9150(96)06050-9

Cited by 33 publications

(21 citation statements)

References 34 publications

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“…In this regard, the apparent dependence of pericytes on PDGFR-␤ signaling 30,31 raises the likelihood that inhibitors of these tyrosine kinase receptors may disrupt angiogenesis in tumors. 58 Pericytes may promote angiogenesis by secreting basic fibroblast growth factor 59,60 or VEGF. 61 Some VEGFexpressing stromal cells near endothelial sprouts in tumors 62 may indeed be pericytes.…”

Section: Pericytes Associated With Endothelial Sprouts In Tumorsmentioning

confidence: 99%

Abnormalities in Pericytes on Blood Vessels and Endothelial Sprouts in Tumors

Morikawa

Bałuk

Kaidoh

et al. 2002

The American Journal of Pathology

891

703

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Endothelial cells of tumor vessels have well-documented alterations, but it is less clear whether pericytes on these vessels are abnormal or even absent.Here we report that ␣-smooth muscle actin (␣-SMA) and desmin-immunoreactive pericytes were present on >97% of blood vessels viewed by confocal microscopy in 100-m-thick sections of three different spontaneous or implanted tumors in mice. However, the cells had multiple abnormalities. Unlike pericytes on capillaries in normal pancreatic islets, which had desmin but not ␣-SMA immunoreactivity, pericytes on capillary-size vessels in insulinomas in RIP-Tag2 transgenic mice expressed both desmin and ␣-SMA. Furthermore, pericytes in RIP-Tag2 tumors, as well as those in MCa-IV breast carcinomas and Lewis lung carcinomas, had an abnormally loose association with endothelial cells and extended cytoplasmic processes deep into the tumor tissue. ␣-SMA-positive pericytes also covered 73% of endothelial sprouts in RIP-Tag2 tumors and 92% of sprouts in the other tumors. Indeed, pericyte sleeves were significantly longer than the CD31-immunoreactive endothelial cell sprouts themselves in all three types of tumors. All three tumors also contained ␣-SMA-positive myofibroblasts that resembled pericytes but were not associated with blood vessels. We conclude that pericytes are present on most tumor vessels but have multiple abnormalities, including altered expression of marker proteins. In contrast to some previous studies, the almost ubiquitous presence of pericytes on tumor vessels found in the present study may be attributed to our use of both desmin and ␣-SMA

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Section: Pericytes Associated With Endothelial Sprouts In Tumorsmentioning

confidence: 99%

Abnormalities in Pericytes on Blood Vessels and Endothelial Sprouts in Tumors

Morikawa

Bałuk

Kaidoh

et al. 2002

The American Journal of Pathology

891

703

View full text Add to dashboard Cite

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“…Angiogenesis was stimulated by conditioned medium from pericytes, and was inhibited by an antibody to basic FGF. Therefore, pericytes may stimulate angiogenesis via secretion of an FGF-like molecule (Watanabe et al 1997). A previous study suggested that FGF and PDGF have positive feedback effects on each other's signaling.…”

Section: Angiogenic Factorsmentioning

confidence: 99%

Brain Pericytes: Emerging Concepts and Functional Roles in Brain Homeostasis

2010

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Brain pericytes are an important constituent of neurovascular unit. They encircle endothelial cells and contribute to the maturation and stabilization of the capillaries in the brain. Recent studies have revealed that brain pericytes play pivotal roles in a variety of brain functions, such as regulation of capillary flow, angiogenesis, blood brain barrier, immune responses, and hemostasis. In addition, brain pericytes are pluripotent and can differentiate into different lineages similar to mesenchymal stem cells. The brain pericytes are revisited as a key player to maintain brain function and repair brain damage.

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“…PDGF receptor (PDGFR) tyrosine kinases are expressed on the surface of pericytes and smooth muscle cells, and both induce proliferation and contribute to vascular maturation (2,3). FGF receptor (FGFR) tyrosine kinases expressedonthesurfaces ofendothelialcells (EC)andsmooth muscle cells, promote signals for cell proliferation and survival, as well as the development and stabilization of blood vessels (4,5).UponinhibitionoftumorVEGF,PDGF,andFGF may also be upregulated to induce and maintain angiogenic activity (6,7).…”

Section: Introductionmentioning

confidence: 99%

Phase I Dose-Escalation Study and Biomarker Analysis of E7080 in Patients with Advanced Solid Tumors

Yamada

Yamamoto

Yamada

et al. 2011

Clinical Cancer Research

144

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Purpose: E7080, an oral multitargeted receptor tyrosine kinase inhibitor, has antiangiogenic and antitumor activity. This Phase I study investigated maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK), pharmacodynamics (PD), and efficacy in patients with advanced solid tumors. Experimental Design: In this sequential, dose-escalation, open-label study E7080 was administered orally twice daily in a 2-week-on/1-week-off cycle. Plasma angiogenic proteins, circulating endothelial cells (CEC) and circulating progenitor cells (CEP) were measured for biomarker analysis. Results: Twenty-seven patients (median age 53 years, performance status 0/1) were enrolled. E7080 was escalated from 0.5 to 1, 2, 4, 6, 9, 13, 16, and 20 mg bid by conventional 3-patient cohorts. During cycle 1, no grade 3/4 toxicity was observed up to 13 mg bid. DLTs included grade 3 AST/ALT increase in 1 patient at 16 mg bid and grade 3 platelet count decrease in 2 patients at 20 mg bid. The MTD of 13 mg bid was determined. After repeated doses, Cmax and area under the plasma concentration–time curve increased in a dose-dependent manner. After 14 days' treatment, c-kit(+) CEPs and CECs significantly decreased in cycle 1, but c-kit(−) CEPs and CECs did not. Change from baseline in c-kit(+) CEC ratio in cycle 1 and baseline SDF1α, c-kit(+) CEPs and c-kit(+) CEP ratio significantly correlated with the E7080 therapeutic effect. Conclusion: E7080 has manageable toxicity up to 13 mg bid when administered in a 2-week-on/1-week-off cycle and shows preliminary activity for durable disease control. Biomarker analysis suggested antiangiogenic activity correlated with antitumor activity in patients with a wide range of solid tumors. Clin Cancer Res; 17(8); 2528–37. ©2011 AACR.

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Cultured retinal pericytes stimulate in vitro angiogenesis of endothelial cells through secretion of a fibroblast growth factor-like molecule

Cited by 33 publications

References 34 publications

Abnormalities in Pericytes on Blood Vessels and Endothelial Sprouts in Tumors

Abnormalities in Pericytes on Blood Vessels and Endothelial Sprouts in Tumors

Brain Pericytes: Emerging Concepts and Functional Roles in Brain Homeostasis

Phase I Dose-Escalation Study and Biomarker Analysis of E7080 in Patients with Advanced Solid Tumors

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