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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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Histology of normal (+/+) and β1- (−/−) teratomas. Tumors derived from normal ES cells (β1 +/+) and from β1- ES  cells (β1 −/−) were stained with Hematoxylin/Eosin (A and B) and lacZ/eosin (C and D), respectively. Blue, lacZ-positive cells are ES  cell-derived whereas lacZ-negative cells are host-derived stromal cells that have migrated into the tumor tissue. Stars indicate lumina of  glandular structures. Bar, 100 μm.
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Figure 4: Histology of normal (+/+) and β1- (−/−) teratomas. Tumors derived from normal ES cells (β1 +/+) and from β1- ES cells (β1 −/−) were stained with Hematoxylin/Eosin (A and B) and lacZ/eosin (C and D), respectively. Blue, lacZ-positive cells are ES cell-derived whereas lacZ-negative cells are host-derived stromal cells that have migrated into the tumor tissue. Stars indicate lumina of glandular structures. Bar, 100 μm.

Mentions: Hematoxylin/Eosin staining revealed that β1 +/+ teratomas (G101) (Fig. 4 A) and β1 +/− teratomas (not shown) are composed of a variety of differentiated cells and tissues, e.g., glandular epithelium, cartilage, connective tissue, and neuronal cells. β1-Null tumors appeared cell dense and contained fewer cords of fibrotic material (Fig. 4 B). Histochemical analysis of several β1- tumors revealed that many differentiated cells are present in β1- teratomas. ES cell–derived cells could be differentiated by lacZ activity, since the lacZ gene was introduced in the β1 integrin gene and in the genome of the mock-transfected ES cells (Fässler et al., 1995; and data not shown). Mock-transfected, as well as β1 integrin–heterozygous tumors contained large areas devoid of lacZ activity proving their host-derived origin (Fig. 4 C). In contrast, the number of lacZ-negative cells was low in all β1- tumors analyzed (Fig. 4 D) indicating that the migration of normal host cells into mutant tumor tissue is reduced.


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)

Histology of normal (+/+) and β1- (−/−) teratomas. Tumors derived from normal ES cells (β1 +/+) and from β1- ES  cells (β1 −/−) were stained with Hematoxylin/Eosin (A and B) and lacZ/eosin (C and D), respectively. Blue, lacZ-positive cells are ES  cell-derived whereas lacZ-negative cells are host-derived stromal cells that have migrated into the tumor tissue. Stars indicate lumina of  glandular structures. Bar, 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Histology of normal (+/+) and β1- (−/−) teratomas. Tumors derived from normal ES cells (β1 +/+) and from β1- ES cells (β1 −/−) were stained with Hematoxylin/Eosin (A and B) and lacZ/eosin (C and D), respectively. Blue, lacZ-positive cells are ES cell-derived whereas lacZ-negative cells are host-derived stromal cells that have migrated into the tumor tissue. Stars indicate lumina of glandular structures. Bar, 100 μm.
Mentions: Hematoxylin/Eosin staining revealed that β1 +/+ teratomas (G101) (Fig. 4 A) and β1 +/− teratomas (not shown) are composed of a variety of differentiated cells and tissues, e.g., glandular epithelium, cartilage, connective tissue, and neuronal cells. β1-Null tumors appeared cell dense and contained fewer cords of fibrotic material (Fig. 4 B). Histochemical analysis of several β1- tumors revealed that many differentiated cells are present in β1- teratomas. ES cell–derived cells could be differentiated by lacZ activity, since the lacZ gene was introduced in the β1 integrin gene and in the genome of the mock-transfected ES cells (Fässler et al., 1995; and data not shown). Mock-transfected, as well as β1 integrin–heterozygous tumors contained large areas devoid of lacZ activity proving their host-derived origin (Fig. 4 C). In contrast, the number of lacZ-negative cells was low in all β1- tumors analyzed (Fig. 4 D) indicating that the migration of normal host cells into mutant tumor tissue is reduced.

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