Bone Metastasis: Molecular Mechanisms Implicated in Tumour Cell Dormancy in Breast and Prostate Cancer

Quayle, Lewis A.; Ottewell, Penelope D.; Holen, Ingunn

doi:10.2174/1568009615666150506092443

Cited by 33 publications

(19 citation statements)

References 72 publications

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“…24,25 “Seed and soil” theory is well acknowledged for bone metastases: circulating cancer cells (seeds) can accomplish metastasis in the organs, of which microenvironment (soil) is advantageous for their growth. 25,26 PVI was associated with cancer cell invasion from primary location, and was proven to be a high-risk predictor of the BMFS in our study (HR = 4.066, 95% CI 1.186–13.935, P = 0.026).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Chemotherapy-Induced Neutropenia at the First Cycle in Invasive Breast Cancer

Chen²,

Zhang³

et al. 2016

Medicine

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Chemotherapy-induced neutropenia (CIN) was the most apparent side effects of bone marrow suppression with adjuvant chemotherapy. Recently, several studies revealed that CIN may predict better outcomes. However, the researches upon breast cancer were still indefinite.We reviewed the female patients with pathologically diagnosed invasive breast cancer at the First Affiliated Hospital of Wenzhou Medical University, between Jan 2008 and Dec 2010. The lowest neutrophil counts in the second week after the first cycle of chemotherapy were collected. Clinicopathological characteristics and survival rates were compared and analyzed between the CIN group and non-CIN group.The median follow-up time was 62 months. The differences of over-all survival and local recurrence-free survival between the 2 groups were nonsense (P = 0.938, P = 0.695, respectively). But the disease-free survival and distant metastasis-free survival of the CIN group were statically significantly better (HR = 0.391, P = 0.009, and HR = 0.315, P = 0.005, respectively). The bone metastasis-free survival may be responsible for the differences (HR = 0.469, P = 0.005). Subgroup analyses showed the CIN may predict lower bone metastases rates with ER positive status, premenopause or younger age (≤ 40) (P = 0.002, P = 0.004, and P = 0.0001, respectively). Cox analysis showed younger ages, N staging, and the presence of CIN were associated with bone metastasis-free survival independently adjusting to peritumoral vascular invasion (P < 0.05).CIN may predict a decreased recurrence risk of breast cancer, especially bone metastases.

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Section: Discussionmentioning

confidence: 99%

Prognostic Value of Chemotherapy-Induced Neutropenia at the First Cycle in Invasive Breast Cancer

Chen²,

Zhang³

et al. 2016

Medicine

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“…Further, they reported stimulation with Epo upregulated known survival pathway mediators—Akt, Erk, and Bcl-xL—which may explain the mechanism by which BCSC cells achieved protection from chemotherapy [31] . These remain among the possible mechanisms that affect cancer therapy and may impact patient survival, through resistance of DTCs within the bone marrow to current chemotherapeutics [32] .…”

Section: Erythropoietin and The Hsc Nichementioning

confidence: 99%

The role of hematopoietic stem cell niche in prostate cancer bone metastasis

Decker

Jung

Cackowski

et al. 2016

Journal of Bone Oncology

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Approximately 80% of prostate cancers exhibit some degree of bone metastasis. The role of the bone marrow and the hematopoietic stem cell (HSC) niche in attracting metastatic cells and maintaining dormancy of disseminated tumor cells (DTCs) is an increasingly important topic towards the development of novel prostate cancer therapies. This paper reviews aspects of the HSC niche that lead to prostate cancer cell homing and dormancy in the bone marrow. This review also discusses the role of DTCs in the niche environment and discusses the role of erythropoietin in targeting DTCs within the HSC niche.

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“…A key phenomenon related to DTC biology is cancer dormancy [12, 13]. Metastatic relapse often occurs after an extended, apparently disease-free period following primary tumor removal.…”

Section: Introductionmentioning

confidence: 99%

Retrieval of Disseminated Tumor Cells Colonizing the Bone in Murine Breast Cancer Metastasis Models

Welte

Yu²,

Zhang

2015

J Mammary Gland Biol Neoplasia

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In breast cancer, the most frequent site of metastasis is bone. Disseminated tumor cells (DTCs) can be detected in the bone marrow of patients by their expression of epithelial or oncogenic markers [1], and the presence and frequency of these DTCs are associated with poor prognosis. However, many of the details behind this process remain elusive, including the biological properties and fates of these apparently indolent cancer cells. To provide pre-clinical models of DTCs, we have developed a procedure that allows for controlled and enhanced delivery of tumor cells to the bone in animal experiments via injection into the iliac artery of the hind limb [2]. To our surprise, we found that most cancer cells became integrated into the solid bone matrix shortly after arriving in the bone, and only a minority can be flushed out with the bone marrow. Here we describe a method that helps to retrieve DTCs homing to the bone in which we achieve an improved recovery of those tumor cells closely associated with the bone microenvironment. In our view it is especially important to analyze these tumor cell subpopulations, as they may take full advantage of growth-, survival- and immune-protective signals provided by neighbor cells. We also show a pilot study on how this approach may be applied to the analysis of cancer dormancy. Our study suggests that the detection and retrieval of DTCs in clinical studies are incomplete because they are conducted exclusively with bone marrow aspirates.

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Bone Metastasis: Molecular Mechanisms Implicated in Tumour Cell Dormancy in Breast and Prostate Cancer

Cited by 33 publications

References 72 publications

Prognostic Value of Chemotherapy-Induced Neutropenia at the First Cycle in Invasive Breast Cancer

Prognostic Value of Chemotherapy-Induced Neutropenia at the First Cycle in Invasive Breast Cancer

The role of hematopoietic stem cell niche in prostate cancer bone metastasis

Retrieval of Disseminated Tumor Cells Colonizing the Bone in Murine Breast Cancer Metastasis Models

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