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Beta 1 integrin is essential for teratoma growth and angiogenesis.

Bloch W, Forsberg E, Lentini S, Brakebusch C, Martin K, Krell HW, Weidle UH, Addicks K, Fässler R - J. Cell Biol. (1997)

Bottom Line: Furthermore, endothelial cells were always of host-derived origin and formed blood vessels with an irregular inner surface.The formation of a complex vasculature, however, was significantly delayed and of poor quality in beta1- embryoid bodies.Moreover, while vascular endothelial growth factor induced proliferation of endothelial cells as well as an extensive branching of blood vessels in normal embryoid bodies, it had no effect in beta 1- embryoid bodies.

View Article: PubMed Central - PubMed

Affiliation: Institute for Anatomy, University of Cologne, 50931 Cologne, Germany.

ABSTRACT
Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of beta 1 integrin during teratoma formation, we compared teratomas induced by normal and beta1- ES cells. Injection of normal ES cells gave rise to large teratomas. In contrast, beta 1- ES cells either did not grow or formed small teratomas with an average weight of <5% of that of normal teratomas. Histological analysis of beta 1- teratomas revealed the presence of various differentiated cells, however, a much lower number of host-derived stromal cells than in normal teratomas. Fibronectin, collagen I, and nidogen were expressed but, in contrast to normal teratomas, diffusely deposited in beta1- teratomas. Basement membranes were present but with irregular shape and detached from the cell surface. Normal teratomas had large blood vessels with a smooth inner surface, containing both host- and ES cell-derived endothelial cells. In contrast, beta 1- teratomas had small vessels that were loosely embedded into the connective tissue. Furthermore, endothelial cells were always of host-derived origin and formed blood vessels with an irregular inner surface. Although beta 1- deficient endothelial cells were absent in teratomas, beta 1- ES cells could differentiate in vitro into endothelial cells. The formation of a complex vasculature, however, was significantly delayed and of poor quality in beta1- embryoid bodies. Moreover, while vascular endothelial growth factor induced proliferation of endothelial cells as well as an extensive branching of blood vessels in normal embryoid bodies, it had no effect in beta 1- embryoid bodies.

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Analysis of cell  proliferation and apoptosis  in a normal (+/+) teratoma  and a β1- (−/−) teratoma. ES cells were injected  under the skin of the back  and incubated for 21 d. 2 h  before tumor isolation BrdU  was injected intraperitoneally. Incorporated BrdU  was detected using specific  antibodies labeled with FITC  (A and B). Apoptotic cells  were identified by staining  for the presence of free 3′-hydroxyl groups in tissue sections of +/+ and −/− teratomas (C and D). Bar, 100 μm.
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Figure 3: Analysis of cell proliferation and apoptosis in a normal (+/+) teratoma and a β1- (−/−) teratoma. ES cells were injected under the skin of the back and incubated for 21 d. 2 h before tumor isolation BrdU was injected intraperitoneally. Incorporated BrdU was detected using specific antibodies labeled with FITC (A and B). Apoptotic cells were identified by staining for the presence of free 3′-hydroxyl groups in tissue sections of +/+ and −/− teratomas (C and D). Bar, 100 μm.

Mentions: To test whether cell proliferation is reduced in β1- tumors BrdU was injected into tumor-bearing mice. Detection of BrdU in tissue sections with specific antibodies showed that the distribution of replicating cells is similar in normal and β1- teratomas. Some areas in both tumor types contained nests of many proliferating cells, whereas other areas show a homogenous distribution of a few proliferating cells (Fig. 3). This heterogeneity of the tumor architecture results from the wide range of different tissues that form in teratomas. As a consequence, the number of proliferating as well as apoptotic cells varied tremendously from one area to another; normal tumors grown for 10 d had between 84 and 176 BrdU-postive cells per mm2 tissue section and tumors grown for 21 d had between 220 and 279 BrdU-positive cells per mm2 tissue section. In corresponding sections of β1- teratomas, the number of proliferating cells ranged between 42 and 116 cells in 10-d-old teratomas, and between 156 and 265 cells in 21-d-old teratomas. This large range in proliferating cells in both tumor types did not provide a statistically significant difference but a tendency towards a reduced proliferation rate in β1- teratomas.


Beta 1 integrin is essential for teratoma growth and angiogenesis.

Bloch W, Forsberg E, Lentini S, Brakebusch C, Martin K, Krell HW, Weidle UH, Addicks K, Fässler R - J. Cell Biol. (1997)

Analysis of cell  proliferation and apoptosis  in a normal (+/+) teratoma  and a β1- (−/−) teratoma. ES cells were injected  under the skin of the back  and incubated for 21 d. 2 h  before tumor isolation BrdU  was injected intraperitoneally. Incorporated BrdU  was detected using specific  antibodies labeled with FITC  (A and B). Apoptotic cells  were identified by staining  for the presence of free 3′-hydroxyl groups in tissue sections of +/+ and −/− teratomas (C and D). Bar, 100 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139829&req=5

Figure 3: Analysis of cell proliferation and apoptosis in a normal (+/+) teratoma and a β1- (−/−) teratoma. ES cells were injected under the skin of the back and incubated for 21 d. 2 h before tumor isolation BrdU was injected intraperitoneally. Incorporated BrdU was detected using specific antibodies labeled with FITC (A and B). Apoptotic cells were identified by staining for the presence of free 3′-hydroxyl groups in tissue sections of +/+ and −/− teratomas (C and D). Bar, 100 μm.
Mentions: To test whether cell proliferation is reduced in β1- tumors BrdU was injected into tumor-bearing mice. Detection of BrdU in tissue sections with specific antibodies showed that the distribution of replicating cells is similar in normal and β1- teratomas. Some areas in both tumor types contained nests of many proliferating cells, whereas other areas show a homogenous distribution of a few proliferating cells (Fig. 3). This heterogeneity of the tumor architecture results from the wide range of different tissues that form in teratomas. As a consequence, the number of proliferating as well as apoptotic cells varied tremendously from one area to another; normal tumors grown for 10 d had between 84 and 176 BrdU-postive cells per mm2 tissue section and tumors grown for 21 d had between 220 and 279 BrdU-positive cells per mm2 tissue section. In corresponding sections of β1- teratomas, the number of proliferating cells ranged between 42 and 116 cells in 10-d-old teratomas, and between 156 and 265 cells in 21-d-old teratomas. This large range in proliferating cells in both tumor types did not provide a statistically significant difference but a tendency towards a reduced proliferation rate in β1- teratomas.

Bottom Line: Furthermore, endothelial cells were always of host-derived origin and formed blood vessels with an irregular inner surface.The formation of a complex vasculature, however, was significantly delayed and of poor quality in beta1- embryoid bodies.Moreover, while vascular endothelial growth factor induced proliferation of endothelial cells as well as an extensive branching of blood vessels in normal embryoid bodies, it had no effect in beta 1- embryoid bodies.

View Article: PubMed Central - PubMed

Affiliation: Institute for Anatomy, University of Cologne, 50931 Cologne, Germany.

ABSTRACT
Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of beta 1 integrin during teratoma formation, we compared teratomas induced by normal and beta1- ES cells. Injection of normal ES cells gave rise to large teratomas. In contrast, beta 1- ES cells either did not grow or formed small teratomas with an average weight of <5% of that of normal teratomas. Histological analysis of beta 1- teratomas revealed the presence of various differentiated cells, however, a much lower number of host-derived stromal cells than in normal teratomas. Fibronectin, collagen I, and nidogen were expressed but, in contrast to normal teratomas, diffusely deposited in beta1- teratomas. Basement membranes were present but with irregular shape and detached from the cell surface. Normal teratomas had large blood vessels with a smooth inner surface, containing both host- and ES cell-derived endothelial cells. In contrast, beta 1- teratomas had small vessels that were loosely embedded into the connective tissue. Furthermore, endothelial cells were always of host-derived origin and formed blood vessels with an irregular inner surface. Although beta 1- deficient endothelial cells were absent in teratomas, beta 1- ES cells could differentiate in vitro into endothelial cells. The formation of a complex vasculature, however, was significantly delayed and of poor quality in beta1- embryoid bodies. Moreover, while vascular endothelial growth factor induced proliferation of endothelial cells as well as an extensive branching of blood vessels in normal embryoid bodies, it had no effect in beta 1- embryoid bodies.

Show MeSH
Related in: MedlinePlus