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Interactions Between Disseminated Tumor Cells and Bone Marrow Stromal Cells Regulate Tumor Dormancy.

ABSTRACT: PURPOSE OF REVIEW:To succinctly summarize recent findings concerning dormancy regulating interactions between bone marrow stromal cells and disseminated tumor cells. RECENT FINDINGS:Recent studies have highlighted roles of the bone marrow microenviroment, including osteoblasts, mesenchymal stem cells (MSCs), and endothelial cells, in inducing or maintaining cancer cell dormancy. Key pathways of interest include: osteoblast-induced transforming growth factor (TGF)-?2 signaling, transfer of MSC-derived exosomes containing dormancy inducing microRNA, cancer cell cannibalism of MSCs, and endothelial cell secretion of thrombospondin 1 (TSP1). The bone marrow is a common site of metastatic disease recurrence following a period of cancer cell dormancy. Understanding why disseminated tumor cells enter into dormancy and later resume cell proliferation and growth is vital to developing effective therapeutics against these cells. The bone marrow stroma and the various pathways through which it participates in crosstalk with cancer cells are essential to furthering understanding of how dormancy is regulated.

SUBMITTER: Widner DB

PROVIDER: S-EPMC6156930 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Interactions Between Disseminated Tumor Cells and Bone Marrow Stromal Cells Regulate Tumor Dormancy.

Widner D Brooke DB Park Sun H SH Eber Matthew R MR Shiozawa Yusuke Y

Current osteoporosis reports 20181001 5

<h4>Purpose of review</h4>To succinctly summarize recent findings concerning dormancy regulating interactions between bone marrow stromal cells and disseminated tumor cells.<h4>Recent findings</h4>Recent studies have highlighted roles of the bone marrow microenviroment, including osteoblasts, mesenchymal stem cells (MSCs), and endothelial cells, in inducing or maintaining cancer cell dormancy. Key pathways of interest include: osteoblast-induced transforming growth factor (TGF)-β2 signaling, tra ...[more]

PMID: 30128835

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Project description:BackgroundCancer metastasis is the primary cause of cancer-related deaths and remains incurable. Current clinical methods for predicting metastatic recurrence are not sensitive enough to detect individual cancer cells in the body; therefore, current efforts are directed toward liquid biopsy-based assays to capture circulating and disseminated tumor cells (CTCs and DTCs) in the blood and bone marrow, respectively. The most promising strategy is fluorescence-based immunostaining using cancer cell-specific markers. However, despite recent efforts to develop robust processing and staining platforms, results from these platforms have been discordant among groups, particularly for DTC detection. While the choice of cancer cell-specific markers is a large factor in this discordance, we have found that marker-independent factors causing false signal are just as critical to consider. Bone marrow is particularly challenging to analyze by immunostaining because endogenous immune cell properties and bone marrow matrix components typically generate false staining. For immunostaining of whole tumor tissue containing ample cancer cells, this background staining can be overcome. Application of fluorescent-based staining for rare cells, however, is easily jeopardized by immune cells and autofluorescence that lead to false signal.ResultsWe have specifically found two types of background staining in bone marrow samples: autofluorescence of the tissue and non-specific binding of secondary antibodies. We systematically optimized a basic immunofluorescence protocol to eliminate this background using cancer cells spiked into human bone marrow. This enhanced the specificity of automated scanning detection software. Our optimized protocol also outperformed a commercial rare cell detection protocol in detecting candidate DTCs from metastatic patient bone marrow.ConclusionsRobust optimization to increase the signal-to-noise ratio of immunofluorescent staining of bone marrow is required in order to achieve the necessary sensitivity and specificity for rare cell detection. Background immunofluorescent staining in bone marrow causes uncertainty and inconsistency among investigators, which can be overcome by systematically addressing each contributing source. Our optimized assay eliminates sources of background signal, and is adaptable to automated staining platforms for high throughput analysis.

Dataset Information

Interactions Between Disseminated Tumor Cells and Bone Marrow Stromal Cells Regulate Tumor Dormancy.

Publications

Interactions Between Disseminated Tumor Cells and Bone Marrow Stromal Cells Regulate Tumor Dormancy.

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