AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective

Abstract

Metastases resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His “seed and soil” hypothesis was substantiated a century later with experimental studies and numerous reports have confirmed these seminal observations. Inarguably, an improved understanding of the metastatic process and the attributes of the cells selected by this process are critical to the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, such that metastasis prevention may not be relevant, and treatment of systemic disease, as well as the identity of patients with early disease, should be our goal. During the last three decades, revitalized research has focused on new discoveries in the biology of metastasis. While our understanding of the molecular events that regulate metastasis has improved; nonetheless, the relevant contributions and timing of molecular lesion(s) potentially involved in its pathogenesis remain unclear. The history of pioneering observations and discussion of current controversies should help investigators understand the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and allow for the design of successful therapy.

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

“…The incidence of breast cancer accounts for 7-8% of the total number of malignant tumors (25). Metastatic progression of breast cancer is a complex and clinically daunting process (26)(27)(28)(29). Breast cancer is both genetically and histopathologically heterogeneous.…”

Prognostic Role of C-reactive Protein in Gastric Cancer: A Meta-analysis

“…However, we have to mention that the statistical results on heterogeneity cannot fully reflect the clinical heterogeneity. In our study, we have to consider "TNM stage" as one of the possible source of heterogeneity as the patients in stage IV differ greatly from those in earlier stage: (1) Unlike the patients in earlier stage, gastric cancer patients in stage IV with distant metastasis have lost the opportunity for operation and mostly have to receive palliative therapies (Catalano et al, 2009) and the difference in treatment contributes greatly to the different outcomes; (2) The patients in stage IV are usually in poor physical condition, suffering weight loss, vomiting, poor oral intake caused by gastrointestinal (GI) obstruction, and the eventually cachexia, while patients in earlier stage usually experience less complications and have better nutritional status (Gencer et al, 2009); (3) Tumors with distant metastasis have already undergone a series of changes in a molecular biological level, triggered a sequence of discrete steps such as so-called invasion-metastasis cascade (Talmadge et al, 2010), showing more malignant biological behavior, which results in the clinical heterogeneity between patients in stage IV and earlier stage. Besides the "TNM stage", "max follow-up period" is also considered another potential source of heterogeneity.…”

Exosomes Released by Melanoma Cells Prepare Sentinel Lymph Nodes for Tumor Metastasis

“…In accordance with the "seed and soil" hypothesis for example cancer stem cells or metastatic cells function as "seeds" and a particular organ microenvironment or niche serves as the "soil" (1)(2)(3). Potential sites for remote tumor implantation might thus be prepared well ahead of actual metastasis (4).…”