Phenotypic Heterogeneity and Metastasis

  • James E. Talmadge
  • I. J. Fidler


The movement of tumor cells from a primary neoplasm to distant organs and the subsequent outgrowth of metastases is the most devastating aspect of cancer. Metastasis is defined as “the transfer of disease from one organ, or part, to another not directly connected to it. It may be due either to the transfer of pathogenic organisms, or to transfer of cells as in malignant tumors.”1 Metastasis involves the release of cells from the primary tumor, dissemination to distant sites, arrest in the microcirculation of organs, extravasation and infiltration into the stroma of those organs, and the survival and growth, with concomitant neovascularization, into new tumor foci (Fig. 1). The outcome of this process is dependent on both host factors and tumor cell properties, and the balance and individual phenotypes of these interactions vary among tumor systems. The precise mechanisms involved in each of the steps are still not clear; however, recent work has clarified some aspects of the processes involved. Although our understanding of the pathogenesis of metastasis has evolved, a concomitant improvement in the treatment of metastatic disease from the major solid tumors of man has not occurred. Despite major advances in general patient care, in surgical techniques, and in adjuvant therapies, most deaths from cancer are caused by the growth of metastases that are resistant to therapy. In most patients, by the time of diagnosis of primary malignant neoplasms (excluding skin cancers), metastasis may well have occurred.2–5 Metastasis can be located in different organs and in different anatomic locations within the same organ. These aspects exert a significant influence on the response of tumor cells to therapy and the efficiency of delivery of anticancer drugs to tumor foci in amounts sufficient to destroy tumor cells without concomitant host toxicity.3 The biggest obstacle to the effective treatment of metastases is, however, the nonuniformity of cells populating both primary and metastatic neoplasms.


Tumor Cell Melanoma Cell Metastatic Tumor Cell Phenotypic Heterogeneity Tumor Embolus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • James E. Talmadge
    • 1
  • I. J. Fidler
    • 2
  1. 1.Smith Kline & French Laboratories, Research and Development DivisionImmunology and Antiinfectives Therapy, King of PrussiaUSA
  2. 2.Department of Cell Biology, M. D. Anderson Hospital and Tumor InstituteUniversity of Texas System Cancer CenterHoustonUSA

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