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The angiogenic response is dictated by beta3 integrin on bone marrow-derived cells.

Feng W, McCabe NP, Mahabeleshwar GH, Somanath PR, Phillips DR, Byzova TV - J. Cell Biol. (2008)

Bottom Line: Angiogenesis is dependent on the coordinated action of numerous cell types.Here, we show that although this receptor is present on most vascular and blood cells, the key regulatory function in tumor and wound angiogenesis is performed by beta(3) integrin on bone marrow-derived cells (BMDCs) recruited to sites of neovascularization.Thus, beta(3) integrin has the potential to control processes such as tumor growth and wound healing by regulating BMDC recruitment to sites undergoing pathological and adaptive angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

ABSTRACT
Angiogenesis is dependent on the coordinated action of numerous cell types. A key adhesion molecule expressed by these cells is the alpha(v)beta(3) integrin. Here, we show that although this receptor is present on most vascular and blood cells, the key regulatory function in tumor and wound angiogenesis is performed by beta(3) integrin on bone marrow-derived cells (BMDCs) recruited to sites of neovascularization. Using knockin mice expressing functionally stunted beta(3) integrin, we show that bone marrow transplantation rescues impaired angiogenesis in these mice by normalizing BMDC recruitment. We demonstrate that alpha(v)beta(3) integrin enhances BMDC recruitment and retention at angiogenic sites by mediating cellular adhesion and transmigration of BMDCs through the endothelial monolayer but not their release from the bone niche. Thus, beta(3) integrin has the potential to control processes such as tumor growth and wound healing by regulating BMDC recruitment to sites undergoing pathological and adaptive angiogenesis.

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Identification of tumor infiltrating BMDCs. (A) Immunofluorescent detection of GFP (a and d) and CD45 (Ab and Ae) along with the merged image (Ac and Af). Sections are of B16F10 origin in WT mice after BMT with WT/GFP (a–c) or DiYF/GFP (d–f) donor marrow. (B) Immunofluorescent detection of GFP (green) and F4/80 (red) in B16F10 tumor sections from WT mice after BMT with WT/GFP (a) or DiYF/GFP (c) donor marrow. Blood vessels marked as V. (b and d) Higher magnifications of enclosed boxes in a and c, respectively. (C) Immunofluorescent detection of CD45+F4/80+Gr-1+CD3 (a and e) and GFP (b and f) along with merged images of B16F10 (c and g) and RM1 (d and h) tumor sections from WT mice after BMT with WT/GFP (a–c) or DiYF/GFP (e–h) donor marrow. Arrows indicate GFP-positive cells that are negative for CD45+F4/80+Gr-1+CD3. Bars, 100 μm.
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fig5: Identification of tumor infiltrating BMDCs. (A) Immunofluorescent detection of GFP (a and d) and CD45 (Ab and Ae) along with the merged image (Ac and Af). Sections are of B16F10 origin in WT mice after BMT with WT/GFP (a–c) or DiYF/GFP (d–f) donor marrow. (B) Immunofluorescent detection of GFP (green) and F4/80 (red) in B16F10 tumor sections from WT mice after BMT with WT/GFP (a) or DiYF/GFP (c) donor marrow. Blood vessels marked as V. (b and d) Higher magnifications of enclosed boxes in a and c, respectively. (C) Immunofluorescent detection of CD45+F4/80+Gr-1+CD3 (a and e) and GFP (b and f) along with merged images of B16F10 (c and g) and RM1 (d and h) tumor sections from WT mice after BMT with WT/GFP (a–c) or DiYF/GFP (e–h) donor marrow. Arrows indicate GFP-positive cells that are negative for CD45+F4/80+Gr-1+CD3. Bars, 100 μm.

Mentions: Studies using models of ischemia have shown that the majority of BMDCs recruited to sites of insult are leukocytes, macrophages, T lymphocytes, and fibroblasts (Ziegelhoeffer et al., 2004). By costaining B16F10 tumor sections for GFP and CD45, a marker for leukocytes or hematopoietic cells, including hematopoietic progenitor/stem cells except erythrocytes and platelets, we found that BM-derived GFP+ cells were frequently CD45 positive (Fig. 5 A) with the extent of GFP+CD45+ double positive cells in DiYF/GFP→WT mice reduced in comparison to that of WT/GFP→WT mice. This alludes to an essential role for β3 integrin signaling in the recruitment of CD45+ cells from BM into sites of angiogenesis.


The angiogenic response is dictated by beta3 integrin on bone marrow-derived cells.

Feng W, McCabe NP, Mahabeleshwar GH, Somanath PR, Phillips DR, Byzova TV - J. Cell Biol. (2008)

Identification of tumor infiltrating BMDCs. (A) Immunofluorescent detection of GFP (a and d) and CD45 (Ab and Ae) along with the merged image (Ac and Af). Sections are of B16F10 origin in WT mice after BMT with WT/GFP (a–c) or DiYF/GFP (d–f) donor marrow. (B) Immunofluorescent detection of GFP (green) and F4/80 (red) in B16F10 tumor sections from WT mice after BMT with WT/GFP (a) or DiYF/GFP (c) donor marrow. Blood vessels marked as V. (b and d) Higher magnifications of enclosed boxes in a and c, respectively. (C) Immunofluorescent detection of CD45+F4/80+Gr-1+CD3 (a and e) and GFP (b and f) along with merged images of B16F10 (c and g) and RM1 (d and h) tumor sections from WT mice after BMT with WT/GFP (a–c) or DiYF/GFP (e–h) donor marrow. Arrows indicate GFP-positive cells that are negative for CD45+F4/80+Gr-1+CD3. Bars, 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2600740&req=5

fig5: Identification of tumor infiltrating BMDCs. (A) Immunofluorescent detection of GFP (a and d) and CD45 (Ab and Ae) along with the merged image (Ac and Af). Sections are of B16F10 origin in WT mice after BMT with WT/GFP (a–c) or DiYF/GFP (d–f) donor marrow. (B) Immunofluorescent detection of GFP (green) and F4/80 (red) in B16F10 tumor sections from WT mice after BMT with WT/GFP (a) or DiYF/GFP (c) donor marrow. Blood vessels marked as V. (b and d) Higher magnifications of enclosed boxes in a and c, respectively. (C) Immunofluorescent detection of CD45+F4/80+Gr-1+CD3 (a and e) and GFP (b and f) along with merged images of B16F10 (c and g) and RM1 (d and h) tumor sections from WT mice after BMT with WT/GFP (a–c) or DiYF/GFP (e–h) donor marrow. Arrows indicate GFP-positive cells that are negative for CD45+F4/80+Gr-1+CD3. Bars, 100 μm.
Mentions: Studies using models of ischemia have shown that the majority of BMDCs recruited to sites of insult are leukocytes, macrophages, T lymphocytes, and fibroblasts (Ziegelhoeffer et al., 2004). By costaining B16F10 tumor sections for GFP and CD45, a marker for leukocytes or hematopoietic cells, including hematopoietic progenitor/stem cells except erythrocytes and platelets, we found that BM-derived GFP+ cells were frequently CD45 positive (Fig. 5 A) with the extent of GFP+CD45+ double positive cells in DiYF/GFP→WT mice reduced in comparison to that of WT/GFP→WT mice. This alludes to an essential role for β3 integrin signaling in the recruitment of CD45+ cells from BM into sites of angiogenesis.

Bottom Line: Angiogenesis is dependent on the coordinated action of numerous cell types.Here, we show that although this receptor is present on most vascular and blood cells, the key regulatory function in tumor and wound angiogenesis is performed by beta(3) integrin on bone marrow-derived cells (BMDCs) recruited to sites of neovascularization.Thus, beta(3) integrin has the potential to control processes such as tumor growth and wound healing by regulating BMDC recruitment to sites undergoing pathological and adaptive angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

ABSTRACT
Angiogenesis is dependent on the coordinated action of numerous cell types. A key adhesion molecule expressed by these cells is the alpha(v)beta(3) integrin. Here, we show that although this receptor is present on most vascular and blood cells, the key regulatory function in tumor and wound angiogenesis is performed by beta(3) integrin on bone marrow-derived cells (BMDCs) recruited to sites of neovascularization. Using knockin mice expressing functionally stunted beta(3) integrin, we show that bone marrow transplantation rescues impaired angiogenesis in these mice by normalizing BMDC recruitment. We demonstrate that alpha(v)beta(3) integrin enhances BMDC recruitment and retention at angiogenic sites by mediating cellular adhesion and transmigration of BMDCs through the endothelial monolayer but not their release from the bone niche. Thus, beta(3) integrin has the potential to control processes such as tumor growth and wound healing by regulating BMDC recruitment to sites undergoing pathological and adaptive angiogenesis.

Show MeSH
Related in: MedlinePlus