Page 21 Complete Your CE Test Online - Click Here trafficking to sites of infection), normal cell growth, and immune responses. Chemokines and their receptors can behave abnormally in cancer, and play important roles in cancer progression and metastases. They can become involved in tumor growth, angiogenesis, evasion of immune detection, and metastasis. For example, chemokines and chemokine receptors that normally induce cell senescence (death of abnormal cells) can be mutated or downregulated in ways that promote tumorigenesis rather than interfere with it. Certain types of cancer cells secrete chemokines that promote growth. Chemokines can support or promote angiogenesis, and forming new blood vessels is a requirement for rapidly-dividing cells and fast-growing tumors [253]. Tumor progression and tumor microenvironments are areas of active research. While it is well known that there are chemokines that normally inhibit tumor cell proliferation, more studies are needed to find out how chemokines and their receptors are co-opted in ways that promote tumor growth and progression. This kind of research might help identify more targets for future treatments. Cancer metastasis Metastasis is a complex process by which certain cancer cells leave their primary site and enter the bloodstream or the lymphatic system to grow elsewhere. Under the microscope, metastatic cancer cells generally look the same as cells of the primary cancer. Moreover, metastatic cancer cells and cells of the original cancer usually have some molecular features in common, such as the expression of certain proteins or the presence of specific genetic mutations [176]. Although a few types of metastatic cancer can be cured with current treatments, it is rare. Treatments are available for patients with metastatic cancer, but the main goal of those treatments is typically to control the growth of the cancer or to palliate symptoms [176]. In some cases, treating metastatic cancer may help prolong life, although each patient must weigh the pros and cons of such treatment, especially if they will have to deal with the side effects of aggressive treatments near the end of life. Nearly all cancers can form metastatic tumors. Although it is rare, even blood and lymphatic system cancers such leukemia, multiple myeloma, and lymphoma can form metastatic tumors, and spread to the lung, heart, central nervous system, and other tissues [176]. Each type of cancer tends to metastasize to common sites The most common sites of cancer metastasis are the bone, liver, and lung. Although most cancers have the ability to spread to many different parts of the body, each type of cancer typically spreads to a few sites much more often than others. The following table shows the most common sites of metastasis, excluding lymph nodes, for some of the more prevalent types of cancer. Table 2. Common cancers and sites of metastasis. Table adapted from National Cancer Institute (2013) [176]. Cancer types Main sites of metastases* Bladder Bone, liver, lung. Breast Bone, brain, liver, lung. Colorectal Liver, lung, peritoneum. Kidney Adrenal gland, bone, brain, liver, lung. Lung Adrenal gland, bone, brain, liver, other lung. Melanoma Bone, brain, liver, lung, skin/muscle. Ovary Liver, lung, peritoneum. Pancreas Liver, lung, peritoneum. Prostate Adrenal gland, bone, liver, lung. Stomach Liver, lung, peritoneum. Thyroid Bone, liver, lung. Uterus Bone, liver, lung, peritoneum, vagina. *These are listed in alphabetical order both down and across. Brain includes the neural tissue of the brain (parenchyma) and the leptomeninges (the two innermost membranes which cover the brain and spinal cord, the arachnoid mater and pia mater; the space between these layers contains the cerebrospinal fluid). Lung includes the main part of the lung (parenchyma as well as the pleura, which covers the lungs and lines the chest cavity). How does cancer spread? A cell’s ability to metastasize is acquired, and requires a series of specific changes. Chemokines and their receptors play a role as well: changes in signaling allow some cells to develop a greater capacity for migration and invasion [253]. Cancer cell metastasis usually involves the following steps [176]: 1. Local invasion: Cancer cells invade nearby normal tissue. 2. Intravasation: Cancer cells invade and move through the walls of nearby lymph vessels or blood vessels. 3. Circulation: Cancer cells move through the lymphatic system and the bloodstream to other parts of the body. 4. Arrest and extravasation: Cancer cells arrest, or stop moving, in capillaries at distant locations. They then invade the walls of the capillaries and migrate into the surrounding tissue (extravasation). 5. Proliferation: Cancer cells multiply at the distant location to form small tumors known as micrometastases. 6. Angiogenesis: Micrometastases stimulate the growth of new blood vessels to obtain a blood supply. A blood supply is needed to obtain the oxygen and nutrients necessary for continued tumor growth. Because cancers of the lymphatic system or the blood system are already present inside lymph vessels, lymph nodes, or blood vessels, not all of these steps are required for their metastasis [176]. The ability of a cancer cell to metastasize successfully depends on: ● ● The cell’s individual properties. ● ● The properties of the noncancerous cells, including immune system cells, present at the primary cancer site. ● ● The properties of the cells it encounters in the lymphatic system or the bloodstream and at the final destination in another part of the body. Not all cancer cells, by themselves, have the ability to metastasize. In addition, noncancerous cells at the primary site may be able to block cancer cell metastasis. Successfully reaching another location in the body does not guarantee that a metastatic tumor will form. Metastatic cancer cells can lie dormant at a distant site for many years before they begin to grow, if they are able to grow at all [176]. Cancer development is a multistep process, and there are many “roadblocks” that may or may not be overcome by the cancer cells. This is why cancer development can take such a long time [176]. Symptoms of metastatic cancer Some people with metastatic tumors do not have symptoms and the metastases are found by X-rays or scans. When symptoms of metastatic cancer occur, their type and frequency depend on the size and location of the metastasis. For example, cancer that spreads to the bone is likely to cause pain and can lead to fractures. Cancer that spreads to the brain can cause a variety of symptoms, including headaches, seizures, and unsteadiness. Shortness of breath or dyspnea on exertion may be signs of lung metastasis. Abdominal swelling or jaundice can suggest that cancer has spread to the liver [176]. Sometimes a patient’s primary cancer is discovered only after a metastatic tumor causes symptoms [176]. In most cases, when a metastatic tumor is found, the primary cancer is also found. The