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Dissecting the metastatic cascade

Nature Reviews Cancer volume 4, pages 448–456 (2004)Cite this article

Key Points

  • In some solid tumours, such as those of the head and neck, the presence of lymph-node metastases is closely linked to the development of distant metastases. In others, such as breast cancer, this association is less pronounced.

  • Gene-expression profiling studies of breast cancer cells indicate that specific molecular pathways are associated with haematogenous dissemination of primary tumour cells, whereas these pathways were not involved with lymphatic dissemination.

  • Disseminated tumour cells found in the bone marrow of patients with various types of solid tumours (for example, breast, colon and lung tumours) can be detected by sensitive immunocytochemical and molecular assays.

  • The presence of disseminated tumour cells in bone marrow predicts the development of overt metastases — both in the bone and other organs.

  • The genetic characterization of single disseminated tumour cells isolated from the bone marrow, along with gene-expression profiling studies of primary tumour cells, indicate that haematogenous dissemination is often a very early event in tumour progression. The cells seem to first disseminate from the early primary lesions and then acquire additional genetic defects.

  • Single disseminated tumour cells in the blood and bone marrow are targets for adjuvant therapy. These cells often show different properties to cells of the primary tumour, so further molecular analysis will provide additional information and will help to develop antimetastatic therapies.

Abstract

Despite recent progress in gene-expression profiling studies, the biology underlying the various patterns of metastasis that are observed in different tumour types remains unclear. The detection and characterization of disseminated tumour cells in patients with cancer has provided important new information about the cascade of metastatic events. This information has important implications for cancer prognosis and for therapy.

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Figure 1: Phenotypic profile of disseminated tumour cells.
Figure 2: Genetic scharacterization of disseminated tumour cells.
Figure 3: Models of the metastatic cascade.

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Acknowledgements

We apologize to those authors whose work we could not cite directly due to space constraints. The authors' research summarized here is mainly supported by the Deutsche Forschungsgemeinschaft (DFG), the Deutsche Krebshilfe, the Roggenbuck-Foundation, the Dutch Cancer Society, the Fanconi Anemia Research Fund and the Netherlands Organization for Scientific Research (NWO). The authors are recipients of a bi-national grant of the DFG and NWO.

Author information

Authors and Affiliations

  1. Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, 202461, Germany

    Klaus Pantel

  2. Department of Otolaryngology/Head-Neck Surgery, Section of Tumor Biology, VU University Medical Center, Amsterdam, 1081HV, The Netherlands

    Ruud H. Brakenhoff

Authors
  1. Klaus Pantel
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Corresponding author

Correspondence to Klaus Pantel.

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Competing interests

Klaus Pantel is the co-founder of Micromet AG (Munich, Germany).

Related links

Related links

DATABASES

Cancer.gov

breast cancer

colon cancer

gastric cancer

head and neck cancer

Entrez Gene

ERBB2

HIF-1α

TP53

uPAR

FURTHER INFORMATION

Dept. Otolaryngology/Head-Neck Surgery, VU University Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf

Minimal Residual Cancer Meeting 2003

Medical Center, Amsterdam

VU Medical Center Microarrays section

Glossary

TUMOUR STAGE

Tumours are evaluated by a pathologist to determine their size and local extension into the surrounding tissue (pT-stage), along with metastases in the surgically removed regional lymph nodes (pN-stage). In addition, patients are screened for the presence of distant metastases (M-stage) by clinical means and radiological methods.

EXPRESSION SIGNATURE

Levels of expression of a given set of genes in a specific tissue, usually assessed by comparing the tissue of interest to a control tissue by microarray analysis.

DISSEMINATED TUMOUR CELLS

Single tumour cells or small cell clusters that can be detected in regional lymph nodes, peripheral blood or organs remote from the primary tumour. These cells are most commonly identified in the bone marrow by sensitive immunocytochemical and molecular techniques.

MICRODISSECTION

Mechanical or laser-assisted dissection of a defined area or specific cells from a tissue section.

CYTOKERATINS

Intermediate filaments of the cytoskeleton that are specifically expressed in epithelial cells.

ILIAC CREST

The outer rim of the pelvic bone that is accessed for needle aspiration of bone marrow.

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Pantel, K., Brakenhoff, R. Dissecting the metastatic cascade. Nat Rev Cancer 4, 448–456 (2004). https://doi.org/10.1038/nrc1370

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