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《Cell》2022,185(20):3753-3769.e18
3.
Tatiana V. Byzova Wes Kim Ronald J. Midura Edward F. Plow 《Experimental cell research》2000,254(2):299
αVβ3, a broadly distributed member of the integrin family of adhesion receptors, has been implicated in a variety of physiological and pathophysiological events, including control of bone density, angiogenesis, apoptosis, tumor growth, and metastasis. Recently, it has been shown that activation of αVβ3, its transition from a low- to a high-affinity/avidity state, influences its recognition of certain ligands. Bone sialoprotein (BSP) is recognized as an important ligand for αVβ3 in processes ranging from bone formation to the homing of metastatic tumor cells. Here, the influence of αVβ3 activation on the adhesion and migration of relevant cells to BSP has been examined. Stimulation of lymphoblastoid, osteoblastoid, and human umbilical vein endothelial cells (HUVEC) with PMA or Mn2+ markedly enhanced αVβ3-dependent adhesion to BSP. αVβ3-mediated migration of HUVEC or osteoblastic cells to BSP was substantially enhanced by stimulation, demonstrating that αVβ3 activation enhances both adhesive and migratory responses. However, adhesion and/or migration of certain tumor cell lines, including M21 melanoma and MDA MB435 and SKBR3 breast carcinoma cell lines, to BSP was constitutively high and was not augmented by αVβ3-activating stimuli. Inhibitors of the intracellular signaling molecules, phosphatidylinositol 3-kinase with wortmannin, hsp90-dependent kinases with geldanamycin, and calpain with calpeptin, but not MAPKK with PD98059, reduced the high spontaneous adhesion and migration of the M21 cells to BSP, consistent with the constitutive activation of the receptor on these tumor cells. These results indicate that the activation state of αVβ3 can regulate cell migration and adhesion to BSP and, by extension, to other ligands of this receptor. The constitutive activation of αVβ3 on neoplastic cells may contribute to tumor growth and metastatic potential. 相似文献
4.
Roberto F. Nicosia Antonio Ottinetti 《In vitro cellular & developmental biology. Plant》1990,26(2):119-128
Summary Rings of rat aorta cultured in Matrigel, a reconstituted gel composed of basement membrane molecules, gave rise to three-dimensional
networks composed of solid cellular cords and occasional microvessels with slitlike lumina. Immunohistochemical and ultrastructural
studies showed that the solid cords were composed of endothelial sprouts surrounded by nonendothelial mesenchymal cells. The
angiogenic response of the aortic rings in Matrigel was compared to that obtained in interstitial collagen, fibrin, or plasma
clot. Morphometric analysis demonstrated that the mean luminal area of the microvascular sprouts and channels was significantly
smaller in Matrigel than in collagen, fibrin, or plasma clot. The percentage of patent microvessels in Matrigel was also markedly
reduced. Autoradiographic studies of3H-thymidine-labeled cultures showed reduced DNA synthesis by developing microvessels in Matrigel. The overall number of solid
endothelial cords and microvessels was lower in Matrigel than in fibrin or plasma clot. A mixed cell population isolated from
Matrigel cultures formed a monolayer in collagen or fibrin-coated dishes but rapidly reorganized into a polygonal network
when plated on Matrigel. The observation that gels composed of basement membrane molecules modulate the canalization, proliferation,
and organization into networks of vasoformative endothelial cells in three-dimensional cultures supports the hypothesis that
the basement membrane is a potent regulator of microvascular growth and morphogenesis.
This work was supported by grants from the W. W. Smith Charitable Trust and grants CA14137 and HL43392 from the National Institutes
of Health, Bethesda, MD. 相似文献
5.
胶质母细胞瘤(glioblastoma,GBM)因组织学异质性、侵袭能力强、术后复发快等问题,致使患者经手术治疗、化疗和放疗后的预后差,总体生存期短。GBM细胞来源外泌体(GBM cell-derived exosome,GBM-exo)能够通过其携带的细胞因子、miRNA、DNA和蛋白质等调节GBM细胞的增殖和迁移,通过血管生成蛋白和非编码RNA促进肿瘤血管生成,通过调节因子、蛋白质和药物靶向免疫检查点等介导肿瘤免疫逃逸,以及通过非编码RNA对抗GBM细胞的耐药性,有望成为个性化治疗GBM的重要靶标,且可以作为GBM的诊断和预后标志物。本文阐述了GBM-exo的制备方法和生物学特征,及其在GBM细胞增殖、血管生成、免疫逃逸和耐药性方面的作用和分子机制,为研发诊治GBM的新策略提供参考。 相似文献
6.
Kasra Moeinabadi-Bidgoli Malihe Rezaee Nikoo Hossein-Khannazer Amirhesam Babajani Hamid Asadzadeh Aghdaei Mandana Kazem Arki Siamak Afaghi Hassan Niknejad Massoud Vosough 《Journal of cellular and molecular medicine》2023,27(6):763-787
Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to “cure” ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100–150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, they are considered as cell-free therapeutics. Besides, exosomes do not rise cell therapy concerns such as teratoma formation, alloreactivity and thrombotic events. In addition, exosomes are stored and utilized more convenient. Interestingly, exosomes could be an ideal complementary therapeutic tool for ischemic disorders. In this review, we discussed therapeutic functions of exosomes in ischemic disorders including angiogenesis induction through various mechanisms with specific attention to vascular endothelial growth factor pathway. Furthermore, different delivery routes of exosomes and different modification strategies including cell preconditioning, gene modification and bioconjugation, were highlighted. Finally, pre-clinical and clinical investigations in which exosomes were used were discussed. 相似文献
7.
Dr. Emrah Ipek Dr. Gamze Sevri Ekren Aşıcı Dr. Erkmen Tuğrul Epikmen Dr. Mürüvvet Abbak Dr. Büşra Kibar Kurt Prof. Dr. Şule Yurdagül Özsoy Prof. Dr. Recai Tunca 《化学与生物多样性》2023,20(7):e202300210
The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-β1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-β1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems. 相似文献
8.
Yamato Kikkawa Kotaro Akaogi Hiroto Mizushima Naoki Yamanaka Makoto Umeda Kaoru Miyazaki 《In vitro cellular & developmental biology. Animal》1996,32(1):46-52
Summary Ladsin is a laminin-like cell-adhesive scatter factor with potent cell motility-stimulating ability and was purified from
serum-free conditioned medium of a malignant human gastric adenocarcinoma cell line STKM-1. To test its possible role in tumor
angiogenesis, we investigated its effect on primary culture of endothelial cells (human umbilical vein endothelial cells)
and endothelial cell line ECV304 in this study. Cell adhesion and motility effects of ladsin were observed in both types of
endothelial cells. In cell-attachment assay, ladsin interacted with integrin α3β1 that was expressed on the endothelial cell
surface. In Boyden chambers, ladsin stimulated both directed and random migration of ECV304 cells. Ladsin induced repair of
artificial wounds generated in ECV304 cell monolayers by stimulating cell migration. Ladsin did not affect the growth rate
of ECV304 cells at a low cell density but significantly increased the saturation cell density. These results suggest that
ladsin may be involved in the adhesion and migration of endothelial cells under some physiological and pathological conditions. 相似文献
9.
James B. Hoying Carl A. Boswell Stuart K. Williams 《In vitro cellular & developmental biology. Animal》1996,32(7):409-419
Summary During angiogenesis, the microvasculature displays both vessel remodeling and expansion under the control of both cellular
and extracellular influences. We have evaluated the role of angiogenic and angiostatic molecules on angiogenesis in anin vitro model that more appropriately duplicates the cellular and extracellular components of this process. Freshly isolated microvessel
fragments from rat adipose tissue (RFMF) were cultured within three-dimensional collagen I gels. These fragments were characterized
at the time of isolation and were composed of vessel segments observed in the microvasculature of fatin situ (i.e., arterioles, venules, and capillaries). Fragments also exhibited characteristic ablumenally associated cells including
smooth muscle cells and pericytes. Finally, fragments were encased in an extracellular matrix composed of collagen type IV
and collagen type I/III. The elongation of microvascular elements was subsequently evaluated using morphologic and immunocytochemical
techniques. The proliferation, migration, and elongation of cellular elements in microvessel fragments from rat adipose tissue
was dependent on initial fragment density, matrix density, and required serum. Inclusion of endothelial cell growth factors
to microvessel fragments from rat adipose tissue 3-D cultures resulted in the accelerated elongation of tube structures and
the expression of von Willebrand factor in cells constituting these tubes. Molecules with reported angiostatic capacity (e.g.,
transforming growth factor and hydrocortisone) inhibited vessel tube elongation.
In vitro methods have been developed to evaluate numerous mechanisms associated with angiogenesis, including endothelial cell proliferation,
migration, and phenotypic modulation. Microvascular endothelial cell fragments described in this study represent anin vitro population of cells that accurately duplicate thein vivo microcirculatory elements of fat. The proliferation of cells and elongation of microvascular elements subsequently observed
in three-dimensional cultures provides anin vitro model of angiogenesis. Microvascular formation in this system results from pre-existing microvessel fragments unlike tube
formation observed when cultured endothelial cells are placed in three-dimensional gels. This form of tube formation from
cultured endothelium is more characteristic of vasculogenesis. Thus, the formation of microvascular elements from microvessel
fragments provides the opportunity to examine the mechanisms regulating angiogenesis in anin vitro system amenable to precise experimental manipulation. 相似文献
10.
Factors involved in capillary growth in the heart 总被引:6,自引:0,他引:6
Olga Hudlická Margaret D. Brown Helene Walter Jacqueline B. Weiss Anita Bate 《Molecular and cellular biochemistry》1995,147(1-2):57-68
Growth of capillaries in the heart occurs under physiological circumstances during endurance exercise training, exposure to high altitude and/or cold, and changes in cardiac metabolism or heart rate elicited by modification of thyroid hormone levels. Capillary growth in all these conditions can be linked with increased coronary blood flow, decreased heart rate, or both. This paper brings evidence that, although increased blood flow due to long-term administration of coronary vasodilators results in capillary growth, a long-term decrease in heart rate induced by electrical bradycardial pacing in rabbits and pigs, or by chronic administration of a bradycardic drug, alinidine, in rats, stimulates capillary growth with little or no change in coronary blood flow. Decreased heart rate results in increased capillary wall tension, increased end-diastolic volume and increased force of contraction, and thus stretch of the capillary wall. This could lead to release of various growth factors possibly stored in the capillary basement membrane. Correlation was found between capillary density (CD) and the levels of low molecular endothelial cell stimulating angiogenic factor (ESAF) both in rabbit and pig hearts with CD increased by pacing. There was no relation between expression of mRNA for basic fibroblast growth factor and CD in sham-operated and paced rabbit hearts. In contrast, mRNA for TGFß was increased in paced hearts, and the possible role of this factor in the regulation of capillary growth induced by bradycardia is discussed. 相似文献