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Review
. 2000;2(6):400-7.
doi: 10.1186/bcr86. Epub 2000 Jul 21.

Molecular biology of breast cancer metastasis. Clinical implications of experimental studies on metastatic inefficiency

Affiliations
Review

Molecular biology of breast cancer metastasis. Clinical implications of experimental studies on metastatic inefficiency

A F Chambers et al. Breast Cancer Res. 2000.

Abstract (V体育ios版)

Recent technological advances have led to an increasing ability to detect isolated tumour cells and groups of tumour cells in patients' blood, lymph nodes or bone marrow. However, the clinical significance of these cells is unclear VSports手机版. Should they be considered as evidence of metastasis, necessitating aggressive treatment, or are they in some cases unrelated to clinical outcome. Quantitative experimental studies on the basic biology of metastatic inefficiency are providing clues that may help in understanding the significance of these cells. This understanding will be of use in guiding clinical studies to assess the significance of isolated tumour cells and micrometastases in cancer patients. .

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Figures

Figure 1
Figure 1
IVVM images of normal (nontumour-bearing) murine mammary fat pad and lymph node. (a) Mammary fat pad, viewed with IVVM, showing three-dimensional structure of vessels and tissue. Direction of lymphatic flow is indicated by the arrow located within the lymphatic vessel (→). Flow within the adjacent blood vessels (➢) was in the same direction. Another vessel (indicated with open arrowhead), was out of the plane of focus and could be resolved by focusing up and down through the tissue. 200×. (b) The inguinal lymph node (LN) found within mammary fat pad #4 where a large internal mammary vessel (*) branches. 40×.
Figure 2
Figure 2
Cell 'accounting' procedure for quantifying in vivo cell survival and metastatic efficiency. Inert plastic fluorescent microspheres (approximately 10 μm) are included in a cell suspension, in a known cell : microsphere ratio. The suspension is injected intravenously to target an organ (eg mesenteric vein to target liver). The microspheres remain indefinitely where they arrest in the microcirculation, providing a reference marker for the number of cells that originally reached that volume of tissue. Based on cell:microsphere ratios at later times, the percentages of surviving cells can be calculated (see example provided).
Figure 3
Figure 3
In vivo detection of solitary mammary carcinoma cells in murine experimental metastasis model. (a) Solitary murine mammary carcinoma (D2.OR) cells (→), fluorescently labelled, are present within normal liver tissue 11 weeks after intravenous injection to target the liver. In close proximity to the cells is a fluorescent 'accounting' microsphere (➢), approximately 10 μm in diameter. The image was obtained by IVVM using epifluorescence plus transillumination. (b) Similar solitary mammary carcinoma cell (→ ; ~ 10-15 μm in diameter) in murine liver, 11 weeks after injection, detected by haematoxylin and eosin staining.
Figure 4
Figure 4
Summary of observations regarding efficiency of specific steps in metastasis, and their dependence on the degree of malignancy of the cells. Conclusions are based on specific experimental results presented in the text.
Figure 5
Figure 5
Isolated breast cancer cell and micrometastasis in sentinel lymph node. (a) Individual isolated tumour cell (→) and (b) small micrometastatic group of tumour cells (→) in the sentinel lymph node of two different breast cancer patients, as detected with anticytokeratin (AE1/AE3) antibodies (400×). The clinical relevance of (a) versus (b) is at present unclear.

References

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