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Bone marrow microenvironment and tumor progression.

Chantrain CF, Feron O, Marbaix E, DeClerck YA - Cancer Microenviron (2008)

Bottom Line: First, the bone marrow actively recruits circulating tumor cells where they find a sanctuary rich in growth factors and cytokines that promote their proliferation and survival.The importance of this new knowledge cannot be underestimated considering that the vast majority of cancer treatments such as cytotoxic and myeloablative chemotherapy, bone marrow transplantation and radiation therapy inflict a trauma to the bone marrow microenvironment.How such trauma affects the influence that the bone marrow microenvironment exerts on cancer is still poorly understood.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Pediatrics, Universite Catholique de Louvain, Brussels, Belgium.

ABSTRACT
The bone marrow constitutes an unique microenvironment for cancer cells in three specific aspects. First, the bone marrow actively recruits circulating tumor cells where they find a sanctuary rich in growth factors and cytokines that promote their proliferation and survival. When in the bone marrow, tumor cells profoundly affect the homeostasis of the bone and the balance between osteogenesis and osteolysis. As a consequence, growth and survival factors normally sequestered into the bone matrix are released, further fueling cancer progression. Second, tumor cells actively recruit bone marrow-derived precursor cells into their own microenvironment. When in the tumors, these bone marrow-derived cells contribute to an inflammatory reaction and to the formation of the tumor vasculature. Third, bone marrow-derived cells can home in distant organs, where they form niches that attract circulating tumor cells. Our understanding of the contribution of the bone marrow microenvironment to cancer progression has therefore dramatically improved over the last few years. The importance of this new knowledge cannot be underestimated considering that the vast majority of cancer treatments such as cytotoxic and myeloablative chemotherapy, bone marrow transplantation and radiation therapy inflict a trauma to the bone marrow microenvironment. How such trauma affects the influence that the bone marrow microenvironment exerts on cancer is still poorly understood. In this article, the reciprocal relationship between the bone marrow microenvironment and tumor cells is reviewed, and its potential impact on cancer therapy is discussed.

No MeSH data available.


Related in: MedlinePlus

VEGFR-1 and 2 positive precursor cells are released from the bone marrow. HSC are retained in the endosteal niche by a combination of cell–cell (Tie-2/angio-1), cell-matrix (α4β1/osteopontin) and receptor–ligand (CXCR-4/SDF-1) interactions. The mobilization of these cells toward the vascular niche and their release in the peripheral blood is in part controlled by MMP-9 which (1) degrades SDF-1, (2) degrades osteopontin, (3) solubilizes cKit-L and (4) degrades the basement membrane
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Fig1: VEGFR-1 and 2 positive precursor cells are released from the bone marrow. HSC are retained in the endosteal niche by a combination of cell–cell (Tie-2/angio-1), cell-matrix (α4β1/osteopontin) and receptor–ligand (CXCR-4/SDF-1) interactions. The mobilization of these cells toward the vascular niche and their release in the peripheral blood is in part controlled by MMP-9 which (1) degrades SDF-1, (2) degrades osteopontin, (3) solubilizes cKit-L and (4) degrades the basement membrane

Mentions: The fate of BMDSC, in particular HSC, is controlled by the microenvironment in the bone marrow. This microenvironment is made of specific niches that provide support for the proliferation and maintenance of stem cells [24]. Interactions between stem cells and their microenvironment regulate their maintenance, proliferation, differentiation and migration into the blood circulation (Fig. 1). Distinct niches have been anatomically and physiologically defined within the bone marrow [25, 26]. In the endosteal region, osteoblasts and other mesenchymal-derived stromal cells such as reticular cells, fibroblasts and adipocytes constitute the osteoblastic niche that supports the maintenance of HSC in a quiescent and undifferentiated state. Alteration of normal osteoblastic function results in a decrease of hematopoiesis and vice versa expansion of osteoblasts is associated with an increased number of HSC in the bone marrow [27, 28]. In the central region of the bone marrow, EC in sinusoids contribute to the formation of a second compartment defined as the vascular niche. BMDSC are recruited in this niche where they proliferate, differentiate and migrate through the sinusoidal wall [26]. Thus whereas the osteoblastic niche promotes the maintenance of a pool of undifferentiated stem cells, the vascular niche promotes the release of differentiated and mature hematopoietic cells.Fig. 1


Bone marrow microenvironment and tumor progression.

Chantrain CF, Feron O, Marbaix E, DeClerck YA - Cancer Microenviron (2008)

VEGFR-1 and 2 positive precursor cells are released from the bone marrow. HSC are retained in the endosteal niche by a combination of cell–cell (Tie-2/angio-1), cell-matrix (α4β1/osteopontin) and receptor–ligand (CXCR-4/SDF-1) interactions. The mobilization of these cells toward the vascular niche and their release in the peripheral blood is in part controlled by MMP-9 which (1) degrades SDF-1, (2) degrades osteopontin, (3) solubilizes cKit-L and (4) degrades the basement membrane
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654350&req=5

Fig1: VEGFR-1 and 2 positive precursor cells are released from the bone marrow. HSC are retained in the endosteal niche by a combination of cell–cell (Tie-2/angio-1), cell-matrix (α4β1/osteopontin) and receptor–ligand (CXCR-4/SDF-1) interactions. The mobilization of these cells toward the vascular niche and their release in the peripheral blood is in part controlled by MMP-9 which (1) degrades SDF-1, (2) degrades osteopontin, (3) solubilizes cKit-L and (4) degrades the basement membrane
Mentions: The fate of BMDSC, in particular HSC, is controlled by the microenvironment in the bone marrow. This microenvironment is made of specific niches that provide support for the proliferation and maintenance of stem cells [24]. Interactions between stem cells and their microenvironment regulate their maintenance, proliferation, differentiation and migration into the blood circulation (Fig. 1). Distinct niches have been anatomically and physiologically defined within the bone marrow [25, 26]. In the endosteal region, osteoblasts and other mesenchymal-derived stromal cells such as reticular cells, fibroblasts and adipocytes constitute the osteoblastic niche that supports the maintenance of HSC in a quiescent and undifferentiated state. Alteration of normal osteoblastic function results in a decrease of hematopoiesis and vice versa expansion of osteoblasts is associated with an increased number of HSC in the bone marrow [27, 28]. In the central region of the bone marrow, EC in sinusoids contribute to the formation of a second compartment defined as the vascular niche. BMDSC are recruited in this niche where they proliferate, differentiate and migrate through the sinusoidal wall [26]. Thus whereas the osteoblastic niche promotes the maintenance of a pool of undifferentiated stem cells, the vascular niche promotes the release of differentiated and mature hematopoietic cells.Fig. 1

Bottom Line: First, the bone marrow actively recruits circulating tumor cells where they find a sanctuary rich in growth factors and cytokines that promote their proliferation and survival.The importance of this new knowledge cannot be underestimated considering that the vast majority of cancer treatments such as cytotoxic and myeloablative chemotherapy, bone marrow transplantation and radiation therapy inflict a trauma to the bone marrow microenvironment.How such trauma affects the influence that the bone marrow microenvironment exerts on cancer is still poorly understood.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology-Oncology, Department of Pediatrics, Universite Catholique de Louvain, Brussels, Belgium.

ABSTRACT
The bone marrow constitutes an unique microenvironment for cancer cells in three specific aspects. First, the bone marrow actively recruits circulating tumor cells where they find a sanctuary rich in growth factors and cytokines that promote their proliferation and survival. When in the bone marrow, tumor cells profoundly affect the homeostasis of the bone and the balance between osteogenesis and osteolysis. As a consequence, growth and survival factors normally sequestered into the bone matrix are released, further fueling cancer progression. Second, tumor cells actively recruit bone marrow-derived precursor cells into their own microenvironment. When in the tumors, these bone marrow-derived cells contribute to an inflammatory reaction and to the formation of the tumor vasculature. Third, bone marrow-derived cells can home in distant organs, where they form niches that attract circulating tumor cells. Our understanding of the contribution of the bone marrow microenvironment to cancer progression has therefore dramatically improved over the last few years. The importance of this new knowledge cannot be underestimated considering that the vast majority of cancer treatments such as cytotoxic and myeloablative chemotherapy, bone marrow transplantation and radiation therapy inflict a trauma to the bone marrow microenvironment. How such trauma affects the influence that the bone marrow microenvironment exerts on cancer is still poorly understood. In this article, the reciprocal relationship between the bone marrow microenvironment and tumor cells is reviewed, and its potential impact on cancer therapy is discussed.

No MeSH data available.


Related in: MedlinePlus