Abstract
The contribution of the tumor stroma to cancer progression has been increasingly recognized. We had previously shown that in human neuroblastoma tumors orthotopically implanted in immunodeficient mice, stromal-derived matrix metalloproteinase-9 (MMP-9) contributes to the formation of a mature vasculature by promoting pericyte recruitment along endothelial cells. Here we show that MMP-9 is predominantly expressed by bone marrow-derived CD45-positive leukocytes. Using a series of bone marrow transplantation experiments in MMP-9+/+ and MMP-9-/- mice xenotransplanted with human neuroblastoma tumors, we show that bone marrow-derived MMP-9 is critical for the recruitment of leukocytes from bone marrow into the tumor stroma and for the integration of bone marrow-derived endothelial cells into the tumor vasculature. Expression of MMP-9 by bone marrow-derived cells in the tumor stroma is also critical for the formation of a mature vasculature and coverage of endothelial cells with pericytes. Furthermore, in primary human neuroblastoma tumor specimens of unfavorable histology, we observed a higher level of tumor infiltration with MMP-9 expressing phagocytic cells and a higher degree of coverage of endothelial cells by pericytes when compared with tumor specimens with a favorable histology. Taken together, the data show that in neuroblastoma, MMP-9 plays a critical role in the recruitment of bone marrow-derived cells to the tumor microenvironment where they positively contribute to angiogenesis and tumor progression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3200-3208 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 65 |
| Issue number | 8 |
| State | Published - Apr 15 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinaae-9 dependent. / Jodele, Sonata; Chantrain, Christophe F.; Blavier, Laurence; Lutzko, Carolyn; Crooks, Gay M.; Shimada, Hiroyuki; Coussens, Lisa; DeClerck, Yves A.
In: Cancer Research, Vol. 65, No. 8, 15.04.2005, p. 3200-3208.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinaae-9 dependent
AU - Jodele, Sonata
AU - Chantrain, Christophe F.
AU - Blavier, Laurence
AU - Lutzko, Carolyn
AU - Crooks, Gay M.
AU - Shimada, Hiroyuki
AU - Coussens, Lisa
AU - DeClerck, Yves A.
PY - 2005/4/15
Y1 - 2005/4/15
N2 - The contribution of the tumor stroma to cancer progression has been increasingly recognized. We had previously shown that in human neuroblastoma tumors orthotopically implanted in immunodeficient mice, stromal-derived matrix metalloproteinase-9 (MMP-9) contributes to the formation of a mature vasculature by promoting pericyte recruitment along endothelial cells. Here we show that MMP-9 is predominantly expressed by bone marrow-derived CD45-positive leukocytes. Using a series of bone marrow transplantation experiments in MMP-9+/+ and MMP-9-/- mice xenotransplanted with human neuroblastoma tumors, we show that bone marrow-derived MMP-9 is critical for the recruitment of leukocytes from bone marrow into the tumor stroma and for the integration of bone marrow-derived endothelial cells into the tumor vasculature. Expression of MMP-9 by bone marrow-derived cells in the tumor stroma is also critical for the formation of a mature vasculature and coverage of endothelial cells with pericytes. Furthermore, in primary human neuroblastoma tumor specimens of unfavorable histology, we observed a higher level of tumor infiltration with MMP-9 expressing phagocytic cells and a higher degree of coverage of endothelial cells by pericytes when compared with tumor specimens with a favorable histology. Taken together, the data show that in neuroblastoma, MMP-9 plays a critical role in the recruitment of bone marrow-derived cells to the tumor microenvironment where they positively contribute to angiogenesis and tumor progression.
AB - The contribution of the tumor stroma to cancer progression has been increasingly recognized. We had previously shown that in human neuroblastoma tumors orthotopically implanted in immunodeficient mice, stromal-derived matrix metalloproteinase-9 (MMP-9) contributes to the formation of a mature vasculature by promoting pericyte recruitment along endothelial cells. Here we show that MMP-9 is predominantly expressed by bone marrow-derived CD45-positive leukocytes. Using a series of bone marrow transplantation experiments in MMP-9+/+ and MMP-9-/- mice xenotransplanted with human neuroblastoma tumors, we show that bone marrow-derived MMP-9 is critical for the recruitment of leukocytes from bone marrow into the tumor stroma and for the integration of bone marrow-derived endothelial cells into the tumor vasculature. Expression of MMP-9 by bone marrow-derived cells in the tumor stroma is also critical for the formation of a mature vasculature and coverage of endothelial cells with pericytes. Furthermore, in primary human neuroblastoma tumor specimens of unfavorable histology, we observed a higher level of tumor infiltration with MMP-9 expressing phagocytic cells and a higher degree of coverage of endothelial cells by pericytes when compared with tumor specimens with a favorable histology. Taken together, the data show that in neuroblastoma, MMP-9 plays a critical role in the recruitment of bone marrow-derived cells to the tumor microenvironment where they positively contribute to angiogenesis and tumor progression.
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UR - http://www.scopus.com/inward/citedby.url?scp=17144430502&partnerID=8YFLogxK
M3 - Article
C2 - 15833851
AN - SCOPUS:17144430502
VL - 65
SP - 3200
EP - 3208
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 8
ER -