Animal studies are costly, time consuming, and subject to several restrictive regulations. However, the metastatic process is one of the research areas in which the in vivo studies remain most relevant (1). In fact, the in vitro studies are not fully predictive of the metastatic behavior of a tumor c ...
Metastasis is a multistep phenomenon, and all steps have to be successfully and consecutively followed through until a clinically manifest metastasis occurs. Although all of these steps have been defined and individual steps can be mimicked in vitro, the rate-limiting step of metastases ...
The growth of metastases is the end result of a multistep process in which cancer cells invade through basement membranes, extravasate into bloodstream or lymphatic vessels, survive transit in the circulation, arrest, and then grow in the new site (1). Tissue culture traits that reliably pred ...
Metastatic spread is generally responsible for the mortality of colorectal cancer patients. There are no adequate treatments for advanced colorectal cancer, and novel therapeutic modalities are urgently required. To this end, valid metastatic models, which accurately mimic the ...
One means of testing a candidate gene for involvement in the metastatic process is to alter the expression of that gene in a tumor cell and then to test the metastatic potential of the altered cells. In designing such experiments, it is crucial to take into account the factor of tumor heterogeneity (1). Some ...
The growth and dissemination of malignant tumors continues to have a devastating impact on people throughout the United States and the rest of the world. In fact, it is estimated that well over a half a million new cases of cancer will be diagnosed per year (1). The most commonly used clinical approaches to t ...
Metastasis is the most devastating aspect of cancer, and the major reason for treatment failure. It is perhaps surprising, therefore, that it is only relatively recently that a wide variety of clinically relevant metastasis models have become generally available. For more than 20 years, the m ...
Invasion occurs when invasion promoter molecules outbalance the function of invasion suppressors (1). Examples of invasion promoters are cell-matrix adhesion molecules, extracellular proteases, and cell motility factors. In normal tissues, positional stability of the cel ...
Metastasis is the major cause of morbidity and death for cancer patients. A critical challenge to clinical and basic scientists is the development of improved prognostic methods to predict the metastatic aggressiveness of a patient’s individual tumor and especially to control local in ...
Basement membranes are specialized extracellular matrices that are comprised of several biological components including collagens, laminins, and proteoglycans. They form thin continuous sheetlike structures that separate epithelial tissues from the adjacent conne ...
Cellular migration is an integral aspect in response to extracellular stimuli, which is fundamental to numerous biological processes such as embryogenesis, inflammation, wound healing, tissue regeneration, and tumor invasion and metastasis (1,2). Abundant studies centered on ...
Tumors usually reach secondary sites via blood vessels or lymphatic vessels. Two processes dependent upon cell migration speed metastasis by reducing the distance between the primary tumor and these vessels. The first process is invasion, in which cancer cells migrate toward the capil ...
The hollow fiber assay is a unique in vivo model that allows simultaneous evaluation of up to 6 different cell lines in 2 physiological separate compartments. It was developed by Hollingshead et al. (1) as a preliminary rapid screen for assessing novel putative chemotherapeutic compounds pr ...
Despite great advances in our understanding of the molecular basis of lung cancer, the efficacy of chemotherapy of lung cancer remains disappointingly low (1). Most of the drugs with established activity against lung cancer were developed using mice with transplantable solid tumors of e ...
The lung offers circulating tumor cells—after their initial development as primary tumors and their selection for metastasis to other organs of patients—several optimal conditions for survival and progression that may be unique to this organ. First, the lung is highly oxygenated and pr ...
Osteosarcoma (1,2) and Ewing’ s sarcoma (3,4) are the two most common primary bone tumors in children. The 2-yr metastasis-free survival rate is 60-65% (5-9) and 41% (10) in patients having osteosarcoma and Ewing’s sarcoma, respectively. These rates have not changed over the past 15 years despite nume ...
The combination of classical mouse genetics with mouse models derived from transgenic and gene-targeting technologies provides new opportunities to elucidate the functional roles of genes in normal and disease processes. Candidate disease genes can be systematically inacti ...
The p53 tumor suppressor gene is the most commonly mutated gene in cancer (1,2) and is mutated in 50% non-small cell lung cancer (NSCLC) and 70% of small cell lung cancer (SCLC) (3). Mutations in p53 commonly reflect exposures to environmental carcinogens, e.g., cigarette smoke and lung cancer or aflato ...
A number of xenograft models have been developed for human lung cancer. These include subcutaneous (sc)-implant models and implantation under the renal capsule, but these models have not been sufficiently representative of the clinical situation (1). The studies of McLemore et al. (2,3) ha ...
In 1930, a German physician wrote a paper in which he most strongly suggested that smoking of cigarettes is a cause of lung cancer (1). In the same year, Mertens (2) published the results of a study in which he had exposed individual mice to cigarette smoke. He used a compressible rubber bulb to force cigarette sm ...

