Limits...
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

Histological examination of bone marrow. Bone marrows of T241-VEGF (A) and T241-vector (B) tumor-bearing mice were stained with H&E. Bone marrows of buffer- (C), anti-VEGFR1- (D), or anti-VEGFR2-(E) treated T241-VEGF-bearing mice were stained with H&E. Arrows in panels A and C-E point to the residual hematopoietic islets. Bone matrix were encircled with dashed lines. Bar in panel A and B = 100 μm. Bar in panels C-E = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2806854&req=5

Figure 5: Histological examination of bone marrow. Bone marrows of T241-VEGF (A) and T241-vector (B) tumor-bearing mice were stained with H&E. Bone marrows of buffer- (C), anti-VEGFR1- (D), or anti-VEGFR2-(E) treated T241-VEGF-bearing mice were stained with H&E. Arrows in panels A and C-E point to the residual hematopoietic islets. Bone matrix were encircled with dashed lines. Bar in panel A and B = 100 μm. Bar in panels C-E = 50 μm.

Mentions: Although VEGF might directly promote extramedullary hematopoiesis in liver and spleen, it was plausible that VEGF-induced extramedullary hematopoiesis echoes defective bone marrow (BM) hematopoiesis and thus represents a compensatory mechanism of BM deficiency. To test this possibility, we histologically examined BM of VEGF tumor-bearing mice. Markedly, VEGF tumor-bearing mice suffered from a severe defect in BM by loosing hematopoiestic cells relative to vector control BM (Fig. 5). Interestingly, VEGFR2 blockade could largely restore VEGF-induced BM defects while VEGFR1 blockade was unable to rescue the defective phenotype (Fig. 5). Based on these findings, it is likely that extramedullary hematopoiesis resulted from defective BM hematopoiesis via compensatory activation of this process in liver and spleen.


Tumor-derived VEGF modulates hematopoiesis.

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

Histological examination of bone marrow. Bone marrows of T241-VEGF (A) and T241-vector (B) tumor-bearing mice were stained with H&E. Bone marrows of buffer- (C), anti-VEGFR1- (D), or anti-VEGFR2-(E) treated T241-VEGF-bearing mice were stained with H&E. Arrows in panels A and C-E point to the residual hematopoietic islets. Bone matrix were encircled with dashed lines. Bar in panel A and B = 100 μm. Bar in panels C-E = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Histological examination of bone marrow. Bone marrows of T241-VEGF (A) and T241-vector (B) tumor-bearing mice were stained with H&E. Bone marrows of buffer- (C), anti-VEGFR1- (D), or anti-VEGFR2-(E) treated T241-VEGF-bearing mice were stained with H&E. Arrows in panels A and C-E point to the residual hematopoietic islets. Bone matrix were encircled with dashed lines. Bar in panel A and B = 100 μm. Bar in panels C-E = 50 μm.
Mentions: Although VEGF might directly promote extramedullary hematopoiesis in liver and spleen, it was plausible that VEGF-induced extramedullary hematopoiesis echoes defective bone marrow (BM) hematopoiesis and thus represents a compensatory mechanism of BM deficiency. To test this possibility, we histologically examined BM of VEGF tumor-bearing mice. Markedly, VEGF tumor-bearing mice suffered from a severe defect in BM by loosing hematopoiestic cells relative to vector control BM (Fig. 5). Interestingly, VEGFR2 blockade could largely restore VEGF-induced BM defects while VEGFR1 blockade was unable to rescue the defective phenotype (Fig. 5). Based on these findings, it is likely that extramedullary hematopoiesis resulted from defective BM hematopoiesis via compensatory activation of this process in liver and spleen.

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