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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

The bone marrow releases VEGFR-1 and 2 pos. precursor cells that promote the development of distant metastases. VEGFR-1 BMDC cells can colonize distant organs via adhesion to fibronectin forming pre-metastatic niches (1). These cells release SDF-1 that attracts CXCR-4 circulating tumor cells (2). When established in these pre-metastatic niches, tumor cells secrete VEGF, PlGF and other cytokines that attract VEGFR-2 pos. BMDC that will contribute to neo-angiogenesis (3)
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Fig4: The bone marrow releases VEGFR-1 and 2 pos. precursor cells that promote the development of distant metastases. VEGFR-1 BMDC cells can colonize distant organs via adhesion to fibronectin forming pre-metastatic niches (1). These cells release SDF-1 that attracts CXCR-4 circulating tumor cells (2). When established in these pre-metastatic niches, tumor cells secrete VEGF, PlGF and other cytokines that attract VEGFR-2 pos. BMDC that will contribute to neo-angiogenesis (3)

Mentions: Until recently, the accepted dogma in metastasis has been that distant organs are first colonized by a sub-population of tumor cells from the primary tumor and that inflammatory cells and EC are then recruited at these sites, where they contribute to angiogenesis and stimulate the proliferation of tumor cells. Recent provocative data however have suggested that the order of these events may well be reversed and that inflammatory cells may be the first ones to reach metastatic sites, forming pre-metastatic niches that attract circulating tumor cells [102]. Using irradiated mice transplanted with EGFP-expressing bone marrow cells and injected subcutaneously with B16 or Lewis Lung tumor cells, Kaplan et al. demonstrated that VEGFR-1 positive BMDC colonize the lung or liver at least a week before tumor cells reach these sites. They also demonstrated that tumor cells only establish metastasis at sites that are precolonized by VEGFR-1+ BMDC and that metastasis could be inhibited by treating the mice with an anti-VEGFR-1 antibody or by removal of VEGFR-1 positive cells from the marrow. The deposition of fibronectin at these pre-metastatic sites seems to be critical in attracting the VEGFR-1 positive cells that express the fibronectin-binding integrin α4β1 (VLA4). It is postulated (Fig. 4) that these cells could then alter the microenvironment leading to the release of chemokines attracting tumor cells like SDF-1. Soon after implantation of tumor cells at these sites, VEGFR-2+ cells are recruited from the bone marrow to promote neo-angiogenesis. Production of VEGF and PlGF by metastatic tumor cells stimulates angiogenesis and the recruitment of additional VEGFR-1+ BMDC. In support of the possibility of a similar mechanism in human cancer metastasis, the presence of VEGFR-1 positive cells in histological sections of human metastatic tumors has been demonstrated. Altogether the data suggest that circulating tumor cells need specific niches to establish themselves and form successful metastatic tumors. The bone marrow therefore not only is a source of local osteoblastic niches that promote the establishment of bone metastases but also of distant pre-metastatic niches that attract circulating tumor cells in distant organs where they find a favorable soil for metastasis [26, 103].Fig. 4


Bone marrow microenvironment and tumor progression.

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

The bone marrow releases VEGFR-1 and 2 pos. precursor cells that promote the development of distant metastases. VEGFR-1 BMDC cells can colonize distant organs via adhesion to fibronectin forming pre-metastatic niches (1). These cells release SDF-1 that attracts CXCR-4 circulating tumor cells (2). When established in these pre-metastatic niches, tumor cells secrete VEGF, PlGF and other cytokines that attract VEGFR-2 pos. BMDC that will contribute to neo-angiogenesis (3)
© Copyright Policy
Related In: Results  -  Collection

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

Fig4: The bone marrow releases VEGFR-1 and 2 pos. precursor cells that promote the development of distant metastases. VEGFR-1 BMDC cells can colonize distant organs via adhesion to fibronectin forming pre-metastatic niches (1). These cells release SDF-1 that attracts CXCR-4 circulating tumor cells (2). When established in these pre-metastatic niches, tumor cells secrete VEGF, PlGF and other cytokines that attract VEGFR-2 pos. BMDC that will contribute to neo-angiogenesis (3)
Mentions: Until recently, the accepted dogma in metastasis has been that distant organs are first colonized by a sub-population of tumor cells from the primary tumor and that inflammatory cells and EC are then recruited at these sites, where they contribute to angiogenesis and stimulate the proliferation of tumor cells. Recent provocative data however have suggested that the order of these events may well be reversed and that inflammatory cells may be the first ones to reach metastatic sites, forming pre-metastatic niches that attract circulating tumor cells [102]. Using irradiated mice transplanted with EGFP-expressing bone marrow cells and injected subcutaneously with B16 or Lewis Lung tumor cells, Kaplan et al. demonstrated that VEGFR-1 positive BMDC colonize the lung or liver at least a week before tumor cells reach these sites. They also demonstrated that tumor cells only establish metastasis at sites that are precolonized by VEGFR-1+ BMDC and that metastasis could be inhibited by treating the mice with an anti-VEGFR-1 antibody or by removal of VEGFR-1 positive cells from the marrow. The deposition of fibronectin at these pre-metastatic sites seems to be critical in attracting the VEGFR-1 positive cells that express the fibronectin-binding integrin α4β1 (VLA4). It is postulated (Fig. 4) that these cells could then alter the microenvironment leading to the release of chemokines attracting tumor cells like SDF-1. Soon after implantation of tumor cells at these sites, VEGFR-2+ cells are recruited from the bone marrow to promote neo-angiogenesis. Production of VEGF and PlGF by metastatic tumor cells stimulates angiogenesis and the recruitment of additional VEGFR-1+ BMDC. In support of the possibility of a similar mechanism in human cancer metastasis, the presence of VEGFR-1 positive cells in histological sections of human metastatic tumors has been demonstrated. Altogether the data suggest that circulating tumor cells need specific niches to establish themselves and form successful metastatic tumors. The bone marrow therefore not only is a source of local osteoblastic niches that promote the establishment of bone metastases but also of distant pre-metastatic niches that attract circulating tumor cells in distant organs where they find a favorable soil for metastasis [26, 103].Fig. 4

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