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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

Tumor cells are recruited by the bone marrow where they alter the osteoblasts and osteoclast balance. SDF-1, which is abundantly present in the bone marrow, attracts CXCR-4 expressing tumor cells. When in the bone marrow tumor cells interact with osteoblasts and osteoclast precursor cells through the production of PTHrP, RANKL and other osteoclast activating factors. Alternatively, tumor cells stimulate MSC to make IL-6. As a result, osteoclasts are activated. Tumor cells also inhibit osteoblast activity and new bone formation by blocking the Wnt pathway via the production of Dkk1. This leads to an increase in bone degradation and release of growth factors
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Fig3: Tumor cells are recruited by the bone marrow where they alter the osteoblasts and osteoclast balance. SDF-1, which is abundantly present in the bone marrow, attracts CXCR-4 expressing tumor cells. When in the bone marrow tumor cells interact with osteoblasts and osteoclast precursor cells through the production of PTHrP, RANKL and other osteoclast activating factors. Alternatively, tumor cells stimulate MSC to make IL-6. As a result, osteoclasts are activated. Tumor cells also inhibit osteoblast activity and new bone formation by blocking the Wnt pathway via the production of Dkk1. This leads to an increase in bone degradation and release of growth factors

Mentions: In many cancer types, circulating tumor cells can be easily identified in the peripheral blood. Although the presence of these cells is often a predictor of poor clinical outcome, it does not necessarily mean that metastatic disease is present or will occur [77, 78]. However these cells can be actively recruited by the bone marrow. The mechanism by which the bone marrow recruits these circulating tumor cells in its microenvironment has been extensively studied (Fig. 3). Central to this process is the production of chemokines by bone marrow stromal cells that act as chemoattractants for tumor cells. Among those, SDF-1 seems again to play the major role. Many tumor cells express the SDF-1 receptor CXCR-4 and thus, like HSC precursor cells, will be attracted into the osteoblastic niche [79–82]. Animal experiments have demonstrated that the migration of CXCR-4 positive breast cancer cells toward the bone marrow can be blocked when cells are pretreated with the CXCR-4 inhibitor AMD 3100 or a blocking antibody against CXCR-4. Downregulation of CXCR-4 in breast cancer cells also inhibits their ability to colonize the bone, and CXCR-4 overexpressing tumor cells have a higher propensity to form bone marrow metastasis when injected intravenously in mice [83, 84]. SDF-1 is however not the only chemokine involved and other chemokines like the ELR-containing CXCL10 have been shown to attract tumor cells in the bone marrow [85]. When tumor cells reach the osteoblastic niche, they do not remain quiescent like HSC and significantly affect the homeostasis of the bone.Fig. 3


Bone marrow microenvironment and tumor progression.

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

Tumor cells are recruited by the bone marrow where they alter the osteoblasts and osteoclast balance. SDF-1, which is abundantly present in the bone marrow, attracts CXCR-4 expressing tumor cells. When in the bone marrow tumor cells interact with osteoblasts and osteoclast precursor cells through the production of PTHrP, RANKL and other osteoclast activating factors. Alternatively, tumor cells stimulate MSC to make IL-6. As a result, osteoclasts are activated. Tumor cells also inhibit osteoblast activity and new bone formation by blocking the Wnt pathway via the production of Dkk1. This leads to an increase in bone degradation and release of growth factors
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654350&req=5

Fig3: Tumor cells are recruited by the bone marrow where they alter the osteoblasts and osteoclast balance. SDF-1, which is abundantly present in the bone marrow, attracts CXCR-4 expressing tumor cells. When in the bone marrow tumor cells interact with osteoblasts and osteoclast precursor cells through the production of PTHrP, RANKL and other osteoclast activating factors. Alternatively, tumor cells stimulate MSC to make IL-6. As a result, osteoclasts are activated. Tumor cells also inhibit osteoblast activity and new bone formation by blocking the Wnt pathway via the production of Dkk1. This leads to an increase in bone degradation and release of growth factors
Mentions: In many cancer types, circulating tumor cells can be easily identified in the peripheral blood. Although the presence of these cells is often a predictor of poor clinical outcome, it does not necessarily mean that metastatic disease is present or will occur [77, 78]. However these cells can be actively recruited by the bone marrow. The mechanism by which the bone marrow recruits these circulating tumor cells in its microenvironment has been extensively studied (Fig. 3). Central to this process is the production of chemokines by bone marrow stromal cells that act as chemoattractants for tumor cells. Among those, SDF-1 seems again to play the major role. Many tumor cells express the SDF-1 receptor CXCR-4 and thus, like HSC precursor cells, will be attracted into the osteoblastic niche [79–82]. Animal experiments have demonstrated that the migration of CXCR-4 positive breast cancer cells toward the bone marrow can be blocked when cells are pretreated with the CXCR-4 inhibitor AMD 3100 or a blocking antibody against CXCR-4. Downregulation of CXCR-4 in breast cancer cells also inhibits their ability to colonize the bone, and CXCR-4 overexpressing tumor cells have a higher propensity to form bone marrow metastasis when injected intravenously in mice [83, 84]. SDF-1 is however not the only chemokine involved and other chemokines like the ELR-containing CXCL10 have been shown to attract tumor cells in the bone marrow [85]. When tumor cells reach the osteoblastic niche, they do not remain quiescent like HSC and significantly affect the homeostasis of the bone.Fig. 3

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