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- Axelsson, Hans, 1972, et al.
(författare)
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Cyclooxygenase inhibition in early onset of tumor growth and related angiogenesis evaluated in EP1 and EP3 knockout tumor-bearing mice
- 2005
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Ingår i: Angiogenesis. - 0969-6970. ; 8:4, s. 339-48
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Tidskriftsartikel (refereegranskat)abstract
- It is well established that prostanoids are essential for local inflammation including cell proliferation and apoptosis. Accordingly, prostaglandin E2 (PGE(2)) is a critical factor in wound healing, tumor invasiveness and progression. Therefore, the aim of the present work was to evaluate effects by PGE(2) on tumor vascular density at early onset of tumor growth where hypoxia is limited. Wild-type mice (C57Bl, C3H/HeN) bearing either MCG-101 tumors or a malignant melanoma (K1735-M2) with either high or insignificant PGE(2) production and subsequently different in sensitivity to cyclooxygenase (COX) inhibition were used. Tumor angiogenesis was estimated by intravital microscopy and immune histochemical analysis in wild type and EP(1) or EP(3) subtype receptor knockout mice (C57Bl). Both MCG-101 and K1735-M2 tumor cells stimulated early outgrowth of tumor vessels in proportion to intrinsic growth rate of tumor cells. Indomethacin had no effects on tumor growth or tumor related vascular area in K1735-M2 bearing mice. By contrast, indomethacin decreased tumor cell proliferation and increased apoptosis in MCG-101 tumors with subsequent adaptation in tumor vascular density. Effects of indomethacin on early growth of MCG-101 tumors were not related to tumor content of bFGF protein, while our earlier studies on long-term tumor growth have shown decreased mRNA levels of bFGF during indomethacin treatment. Early onset of tumor growth was significantly promoted in EP(3)- but not in EP(1)-knockouts, although long-term tumor growth is attenuated in EP(1)-knockouts as reported elsewhere. Our results demonstrate that tumor production of PGE(2) promotes primarily net growth of tumor cells with subsequent adaptations in development of the tumor vasculature. Therefore, it is likely that angiogenesis is not a limiting step at the early onset of tumor growth.
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| 2. |
- Dabrosin, Charlotta, 1961-
(författare)
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Sex steroid regulation of angiogenesis in breast tissue
- 2005
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Ingår i: Angiogenesis. - : Springer Science and Business Media LLC. - 0969-6970 .- 1573-7209. ; 8:2, s. 127-136
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis is essential for normal function in the female reproductive tract and a prerequisite for growth and metastasis of solid tumors. Several factors, both inducers and inhibitors, play essential roles in the regulation of the angiogenic process. Exposure to sex steroids increases the risk of breast cancer but the mechanisms are poorly understood and the importance of angiogenesis in breast carcinogenesis is undefined. In the female reproductive tract ovarian hormones tightly regulate angiogenesis. The breast is also a target organ for sex steroids but very little is known about sex steroid effects on angiogenesis in normal breast tissue and breast cancer. In this review several regulators of angiogenesis, and their relation to sex steroids, in breast tissue are discussed. Increased knowledge in this area is of utmost importance for future therapeutic treatment options and for breast cancer prevention. © Springer 2005.
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| 3. |
- Jensen, Lasse Dahl, et al.
(författare)
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Regulation of endothelial cell migration by amphiphiles - are changes in cell membrane physical properties involved?
- 2007
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Ingår i: Angiogenesis. - : Kluwer Academic Publishers. - 0969-6970 .- 1573-7209. ; 10:1, s. 13-22
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cell (EC) migration is an integral part of angiogenesis and a prerequisite for malignant tumor growth. Recent studies suggest that amphiphilic compounds can regulate migration of bovine aortic ECs by altering the physical properties of the cell membrane lipid bilayers. A number of structurally different amphiphiles thus regulate the migration in quantitative correlation with their effects on the plasma membrane microviscosity. Many amphiphiles that affect EC migration and angiogenesis alter the physical properties of lipid bilayers, suggesting that such a regulatory mechanism may be of general importance. To investigate this notion, we studied the effects of lysophospholipids that inhibit migration of bovine aortic ECs and decrease cell membrane microviscosity, and of other amphiphiles that decrease membrane microviscosity (Triton X-100, octyl-beta-glucoside, arachidonic acid, docosahexaenoic acid, ETYA, capsaicin) on the migration of porcine aortic ECs. We further studied whether the enzyme secretory phospholipase A(2) (sPLA(2)) would affect migration in accordance with the changes in membrane microviscosity induced by its hydrolysis products lysophospholipids and polyunsaturated fatty acids. Arachidonic acid, at low concentrations, promoted cell migration by a mechanism involving metabolic products of this compound. Apart from this effect, all the amphiphiles, as well as sPLA(2), inhibited cell migration. A semi-quantitative analysis found a similar correlation between the effects on migration and on lipid bilayer stiffness measured using gramicidin channels as molecular force transducers. These results suggest that changes in cell membrane physical properties may generally contribute to the effects of amphiphiles on EC migration.
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