title: Tumor-derived VEGF modulates hematopoiesis.
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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute 171 77 Stockholm, Sweden.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, 200030 Shanghai, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute 171 77 Stockholm, Sweden.
authors.forename: Danfang
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute 171 77 Stockholm, Sweden.
authors.forename: Sharon
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute 171 77 Stockholm, Sweden.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao