Metastasis/metastatic

Metastatic breast cancer is not curable, and therapy is intended to palliate symptoms. In most cases, hormonal therapy is the mainstay. While on therapy, patients are monitored monthly for signs of disease progression or metastasis to common sites, such as the bones, brain, or liver. 

Brain metastasis is common in melanoma, and treatment options for brain metastasis include surgery, radiation, and chemotherapy. The choice of therapy depends on the number of metastatic lesions, accessibility of the lesions for surgery, the presence of neurologic symptoms, and the status of extracranial disease. 

In patients with SCC, metastatic spread to the lymph nodes occurs in less than 5%.32 The lymph nodes of the head and neck are the most common sites of metastasis. Patients are still curable with this stage of the disease, but they are at high risk of experiencing regional relapse and distant metastasis to the bones and lungs. As may be expected, survival is decreased compared with patients who do not present with nodal involvement. Factors that may be useful in... 

Walser TC, Rifat S, Ma X, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res 2006 66 7701-7707. 

Li A, Varney ML, Singh RK. Constitutive expression of growth regulated oncogene (gro) in human colon carcinoma cells with different metastatic potential and its role in regulating their metastatic potential. Clin Exp Metastasis 2004 21 571-579. 

Varney ML, Li A, Dave BJ, Bucana CD, Johansson SL, Singh RK. Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different metastatic potential and their role in interleukin-8 (CXCL-8)-mediated modulation of metastatic phenotype. Clin Exp Metastasis 2003 20 723-731. 

Ultrasensitive assays for PSA contribute to the earlier detection of prostate cancer relapse and (or) residual disease in prostatectomized patients as well as the more timely evaluation of response to current therapies. PSA determinations can be useful in detecting metastatic or persistent disease in patients following surgical or medical treatment of prostate cancer. Persistent elevation of PSA following treatment, or an increase in the pretreatment PSA concentrations, is indicative of recurrent or residual disease. Hence, PSA is widely accepted as an aid in the management of prostate cancer patients, and serum levels are most useful when sequential values are obtained and monitored over time. After complete removal of the prostate gland (radical prostatectomy), PSA levels should become very low or undetectable. A rise of the serum PSA level in prostatectomy patients indicates residual prostate tissue, recurrence, or metastasis of the disease (13, 16, 24, 36). 

Urquidi, V., Sloan, D., Kawai, K., Agarwal, D., Woodman, A. C., Tarin, D., Goodison, S. (2002). Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis. Clin. Cancer Res. 8(1), 61-74. 

Approximately 20% of patients with colorectal cancer present with metastatic disease. The most common site of metastasis is the liver, followed by the lungs, and then bones. 

In humans, also, preferential sites exist for the formation of metastasis from various primary tumors [reviewed in Zetter (Zl)]. Thus, bone is a preferred site for metastasis from primary malignancies in breast, prostate, and kidney, while liver is a frequent metastatic site for tumors originating in the colon. Different types of leukemias vary widely in their ability to spread to liver, lymph, bone, and spleen. Some organs, however, are rarely colonized by metastatic growth. These resistant sites include skeletal muscle, heart, and skin. 

Correlation of Certain Proteases with Metastatic Potential in Model Tumor Systems. A variety of different proteases have been found to correlate with metastatic potential in model tumor systems. Many of these early studies were carried out with B16 mouse melanoma cells. Variants of these cells with different metastatic potential have been selected. In separate experiments, total PA activity, CB activity, and collagenase IV activity have all been found to correlate with metastatic potential in these cells (A4, D6). More recently, levels of mRNA for CB have also been found to correlate with metastasis in these melanoma cells (Ql). Correlations also exist between levels of specific proteases and metastatic ability in a number of other model systems see Table 2 (D6). 

Inverse Relationship between Protease Inhibitors and Metastatic Ability. All proteases, apart from possibly CD, appear to be controlled by endogenous inhibitors. In theory, therefore, the ability of malignant cells to produce metastasis could depend not only on the levels of the specific protease, but also on the concentration of relevant endogenous inhibitors. Thus, the presence of high levels of protease inhibitors might inhibit metastasis, while low levels of inhibitors might enhance metastasis. An inverse relationship between a number of specific inhibitors and metastatic potential has now been shown. Some examples of this type of relationship include TIMP-1 in Swiss 3T3 cells (K4), cysteine protease inhibitors in mouse melanoma cells (R6), and an alpha-1-proteinase inhibitor in rat mammary carcinomas (N2). Furthermore, a newly described serine protease inhibitor, known as maspin, was found to be expressed less frequently in advanced human breast cancers compared with early cancers (Z2). 

I. Transfection of Genes Encoding Proteases Enhances Metastasis. Transfection of different cell types with the genes for either uPA or CD confers or enhances the metastatic ability of the recipient cells. This has been shown for uPA in mouse L cells, ras-transformed NIH 3T3 cells, and murine B16 mela-... 

Human cancers vary widely in their ability to produce metastasis. At present, there are no reliable methods to predict metastatic potential. For optimum patient management, however, knowledge of the aggressiveness of a tumor is desirable when deciding which patients should receive adjuvant chemotherapy. This type of information is particularly important for axillary node-negative breast cancer and Dukes B colorectal cancer. 

Since certain proteases are directly involved in cancer invasion and metastasis, levels of these proteases in primary cancers should be strong markers of metastatic potential or poor patient outcome. 

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