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Tumor-derived VEGF modulates hematopoiesis.

Xue Y, Chen F, Zhang D, Lim S, Cao Y - J Angiogenes Res (2009)

Bottom Line: However, little is known about its hematopoietic activity during malignant development and progression.Furthermore, VEGFR1 and VEGFR2 were primarily localized in blood vessels rather than hepatocytes or splenocytes, demonstrating that alteration of angiogenic profiles modulates hematopoiesis in these organs.Stimulation of extramedullary hematopoiesis sheds new light on complex biological functions of VEGF and significantly increases our understanding of molecular mechanisms underlying VEGF-induced tumor growth.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.

ABSTRACT
VEGF-induced angiogenesis significantly contributes to tumor growth, invasion and metastasis. However, little is known about its hematopoietic activity during malignant development and progression. Here we show that in a mouse tumor model, tumor-derived VEGF acts as an endocrine-like hormone to induce extramedullary hematopoiesis by targeting distal organs in the host. In tumor-bearing mice, circulating VEGF induced hepatomegaly and splenomegaly owing to vessel dilation, tortuosity and activation of hematopoiesis. Furthermore, VEGFR1 and VEGFR2 were primarily localized in blood vessels rather than hepatocytes or splenocytes, demonstrating that alteration of angiogenic profiles modulates hematopoiesis in these organs. Stimulation of extramedullary hematopoiesis sheds new light on complex biological functions of VEGF and significantly increases our understanding of molecular mechanisms underlying VEGF-induced tumor growth.

No MeSH data available.


Related in: MedlinePlus

Spleno-extramedullary hematopoiesis. Spleen sections from T241-VEGF and T241-vector tumor-bearing mice were stained with H&E (A and B), or were double stained an anti-Ter119 antibody and propidium iodide (PI) (C and D). Dashed lines in panel B encircle white pulp (WP). RP = red pulp. Hematopietic cells from the erythrocyte lineage were labeled with Ter119 (green) and all cell nuclei were labeled with PI (red). Bar in panel A and B = 100 μm. Bar in C and D = 50 μm.
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Figure 2: Spleno-extramedullary hematopoiesis. Spleen sections from T241-VEGF and T241-vector tumor-bearing mice were stained with H&E (A and B), or were double stained an anti-Ter119 antibody and propidium iodide (PI) (C and D). Dashed lines in panel B encircle white pulp (WP). RP = red pulp. Hematopietic cells from the erythrocyte lineage were labeled with Ter119 (green) and all cell nuclei were labeled with PI (red). Bar in panel A and B = 100 μm. Bar in C and D = 50 μm.

Mentions: Because extramedullary hematopoiesis often occurs in the spleen of mice, we next examined spleens of tumor-bearing mice. Similar to livers, splenomegaly also existed in T241-VEGF tumor-bearing mice [5]. Histological examination showed that apparent borders between the white pulp (WP) and red pulp (RP) under physiological conditions were vanished and were replaced by a mixture of WP and RP without any distinctive borders throughout the entire spleen of T241-VEGF tumor-bearing mice (Fig. 2). Ter119 staining revealed that active hematopoiesis occurred throughout the entire spleen tissue of T241-VEGF tumor-bearing mice (Fig. 2). In markedly contrast, Ter119 positive signals only present in the RP region in the spleen of T241-vector tumor-bearing mice (Fig. 2). These findings show that tumor-derived VEGF significantly modulates extramedullary hematopoiesis in the adult spleen by expansion of RP areas.


Tumor-derived VEGF modulates hematopoiesis.

Xue Y, Chen F, Zhang D, Lim S, Cao Y - J Angiogenes Res (2009)

Spleno-extramedullary hematopoiesis. Spleen sections from T241-VEGF and T241-vector tumor-bearing mice were stained with H&E (A and B), or were double stained an anti-Ter119 antibody and propidium iodide (PI) (C and D). Dashed lines in panel B encircle white pulp (WP). RP = red pulp. Hematopietic cells from the erythrocyte lineage were labeled with Ter119 (green) and all cell nuclei were labeled with PI (red). Bar in panel A and B = 100 μm. Bar in C and D = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2806854&req=5

Figure 2: Spleno-extramedullary hematopoiesis. Spleen sections from T241-VEGF and T241-vector tumor-bearing mice were stained with H&E (A and B), or were double stained an anti-Ter119 antibody and propidium iodide (PI) (C and D). Dashed lines in panel B encircle white pulp (WP). RP = red pulp. Hematopietic cells from the erythrocyte lineage were labeled with Ter119 (green) and all cell nuclei were labeled with PI (red). Bar in panel A and B = 100 μm. Bar in C and D = 50 μm.
Mentions: Because extramedullary hematopoiesis often occurs in the spleen of mice, we next examined spleens of tumor-bearing mice. Similar to livers, splenomegaly also existed in T241-VEGF tumor-bearing mice [5]. Histological examination showed that apparent borders between the white pulp (WP) and red pulp (RP) under physiological conditions were vanished and were replaced by a mixture of WP and RP without any distinctive borders throughout the entire spleen of T241-VEGF tumor-bearing mice (Fig. 2). Ter119 staining revealed that active hematopoiesis occurred throughout the entire spleen tissue of T241-VEGF tumor-bearing mice (Fig. 2). In markedly contrast, Ter119 positive signals only present in the RP region in the spleen of T241-vector tumor-bearing mice (Fig. 2). These findings show that tumor-derived VEGF significantly modulates extramedullary hematopoiesis in the adult spleen by expansion of RP areas.

Bottom Line: However, little is known about its hematopoietic activity during malignant development and progression.Furthermore, VEGFR1 and VEGFR2 were primarily localized in blood vessels rather than hepatocytes or splenocytes, demonstrating that alteration of angiogenic profiles modulates hematopoiesis in these organs.Stimulation of extramedullary hematopoiesis sheds new light on complex biological functions of VEGF and significantly increases our understanding of molecular mechanisms underlying VEGF-induced tumor growth.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.

ABSTRACT
VEGF-induced angiogenesis significantly contributes to tumor growth, invasion and metastasis. However, little is known about its hematopoietic activity during malignant development and progression. Here we show that in a mouse tumor model, tumor-derived VEGF acts as an endocrine-like hormone to induce extramedullary hematopoiesis by targeting distal organs in the host. In tumor-bearing mice, circulating VEGF induced hepatomegaly and splenomegaly owing to vessel dilation, tortuosity and activation of hematopoiesis. Furthermore, VEGFR1 and VEGFR2 were primarily localized in blood vessels rather than hepatocytes or splenocytes, demonstrating that alteration of angiogenic profiles modulates hematopoiesis in these organs. Stimulation of extramedullary hematopoiesis sheds new light on complex biological functions of VEGF and significantly increases our understanding of molecular mechanisms underlying VEGF-induced tumor growth.

No MeSH data available.


Related in: MedlinePlus