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On the adaptation of endosteal stem cell niche function in response to stress.

ABSTRACT: Although the influence of microenvironmental "niche" on the function of a variety of stem cells is undisputed, the details of hematopoietic stem cell/niche interactions at the cellular and molecular level have sparked a continuous debate. We studied the microanatomic partitioning of transplanted normal and alpha4 integrin-deficient Lin-kit+ cells in trabecular and compact bone before and after irradiation and present robust quantitative data on both. We found that (1) the microanatomic distribution of normal highly enriched progenitor cells is random in nonirradiated recipients based on area distribution analyses, (2) in contrast, in irradiated hosts normal cells distribute preferentially near the endosteum, (3) the overall cell seeding efficiency was higher in trabecular versus compact bone both before and after irradiation, and (4) alpha4 integrin-deficient cells not only lodge with reduced overall efficiency confirming previous data, but fail to preferentially partition themselves into endosteal regions in irradiated hosts, as normal cells do. A similar phenotype was observed with cells rendered G(i)-protein signaling incompetent by pertussis toxin treatment, supporting an active stromal-derived factor 1 (SDF-1) gradient near endosteum after irradiation.

SUBMITTER: Jiang Y

PROVIDER: S-EPMC2773492 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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On the adaptation of endosteal stem cell niche function in response to stress.

Jiang Yi Y Bonig Halvard H Ulyanova Tatiana T Chang KaiHsin K Papayannopoulou Thalia T

Blood 20090901 18

Although the influence of microenvironmental "niche" on the function of a variety of stem cells is undisputed, the details of hematopoietic stem cell/niche interactions at the cellular and molecular level have sparked a continuous debate. We studied the microanatomic partitioning of transplanted normal and alpha4 integrin-deficient Lin-kit+ cells in trabecular and compact bone before and after irradiation and present robust quantitative data on both. We found that (1) the microanatomic distribut ...[more]

PMID: 19724056

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Project description:The establishment of bone metastasis remains one of the most frequent complications of patients suffering from advanced breast cancer. Patients with bone metastases experience high morbidity and mortality caused by excessive, tumor-induced and osteoclast-mediated bone resorption. Anti-resorptive treatments, such as bisphosphonates, are available to ease skeletal related events including pain, increased fracture risk, and hypercalcemia. However, the disease remains incurable and 5-year survival rates for these patients are below 25%. Within the bone, disseminated breast cancer cells localize in "metastatic niches," special microenvironments that are thought to regulate cancer cell colonization and dormancy as well as tumor progression and subsequent development into overt metastases. Precise location and composition of this "metastatic niche" remain poorly defined. However, it is thought to include an "endosteal niche" that is composed of key bone cells that are derived from both, hematopoietic stem cells (osteoclasts), and mesenchymal stromal cells (osteoblasts, fibroblasts, adipocytes). Our knowledge of how osteoclasts drive the late stage of the disease is well-established. In contrast, much less is known about the interaction between osteogenic cells and disseminated tumor cells prior to the initiation of the osteolytic phase. Recent studies suggest that mesenchymal-derived cells, including osteoblasts and fibroblasts, play a key role during the early stages of breast cancer bone metastasis such as tumor cell homing, bone marrow colonization, and tumor cell dormancy. Hence, elucidating the interactions between breast cancer cells and mesenchymal-derived cells that drive metastasis progression could provide novel therapeutic approaches and targets to treat breast cancer bone metastasis. In this review we discuss evidences reporting the interaction between tumor cells and endosteal niche cells during the early stages of breast cancer bone metastasis, with a particular focus on mesenchymal-derived osteoblasts and fibroblasts.

Dataset Information

On the adaptation of endosteal stem cell niche function in response to stress.

Publications

On the adaptation of endosteal stem cell niche function in response to stress.

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