Who Let the Cancerous Cells Out?
(Who? Who? Who? Who? Who?)
Discovery of the Protein That Causes Cancer to Spread
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Cancer Awareness Ribbon
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The Cancer
Cancer is generally characterized as the abnormal or out-of-control growth of cell. Normally, cells go through stages of growth, division and death (“Definition of Cancer,”2004). When programmed cell death, apoptosis, does not occur, cancer cells begin to develop. This transpires when damages or mutations to the DNA render the cells incapable of correcting the DNA damage and undergoing apoptosis. Eventually the cancer cells continue to grow and divide then form mass or lumps of abnormal cells called tumors. Tumors that settle in one particular spot and display limited growth are said to be benign while those that move throughout the body are considered dangerous and said to be malignant. This can be directly caused by carcinogens, substances that damage DNA, or a result of a genetic predisposition. Different types of cancer have different signs and symptoms depending on its location, size and extent. Some can be physically apparent through lumps in the breast or testicle, patches in the mouth or tongue or noted changes in a wart or mole. Others are less obvious such as brain tumors. Though indicative of other illnesses as well, it is possible to experience fever, fatigue, excessive sweating, anaemia and unexplained weight loss. If the cancer cells spread, other symptoms can arise such as seizures, coughing of blood and shortness of breath. Extraction of cancer cells and microscopic analysis, otherwise known as biopsies, is a one possible conclusive procedure done to diagnose cancer. When detected at an early stage, cancer can be effectively treated and survival rate is higher. Treatment can be done through surgery, radiation, chemotherapy, hormone therapy or gene therapy(“Cancer,” 2010) .
In the Philippines, as stated by the Department of Health, cancer is the third leading cause of mortality, next to heart diseases and vascular system diseases(Figure 1). Specifically, the foremost types of cancer causing deaths in the country are, in order of killing contribution, cancer of the lung, breast, cervix, liver, colon and rectum, prostate, stomach, oral cavity ovary and leukaemia. Lung cancer ranks number one because of smoking and air pollution. Cancer kills numerous Filipino people because of the general lack of knowledge regarding cancer awareness and prevention. In addition to this, cancer survival rates are usually low since Filipinos have the tendency of seeking medical help only when the cancer is already at advanced stages as brought about by economic or financial problems or fear of being diagnosed with a deadly disease(Emer, 2010).
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Figure 1. Top ten leading causes of mortality in the Philippines, as reported by DOH
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The Stages
In determining the stage of cancer, there are various scales being used. Generally, however, they are arranged according to the degree of severity with the lower values representing less invasive and acute stages of cancer and higher numbers indicating more dangerous and wide spread stages. Establishing the stage of cancer is necessary so that health professionals can strategize on a treatment plan, determine prognosis and to communicate and report accurate findings and results with others(Smith, 2010).
One common scale used in staging cancer employs the numbers 0, I, II, III, and IV to represent progressive severity. 0 means that only a few cancer cells are involved and the succeeding phases represents more advanced cases based on tumor size, extent of growth and spreading(Ever, 2010) . Another scale that is often used in staging cancer is the TNM system. Three separate parameters are used to determine the seerity of the cancer: T-tumor size, N-lymph node involvement and M-for metastasis or degree it has spread to other loctions. Other health professionals employ the summary staging which differentiates stages based on their location: “in situ”-early stage of cancer, “localized”-primarily in one organ and has not yet spread, “regional”-has spread to local lymph nodes and “distant”-has spread to distant organs(Hill, 2010).
In all the scales mentioned, the last and often most critical stage of cancer is when the cancerous cells have spread to other organs or Metastasis(Figure 2).
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Figure 2: Common sites of metastasis and symptoms
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The Proliferation
Metastasis, as mentioned, is when the cells begin to leave the original site of the tumor and migrate to other parts or organs in the body. Generally, the first step in metastasis is the breaking away of the malignant tumor cells from the original site of the tumor. This then attaches and degrades the protein mesh also known as the extracellular matrix (ECM) that separates the tumor and the adjacent tissue surrounding it. Once it has broken the ECM, it escapes via the bloodstream or the lymphatic system and migrates in other organs of the body(Figure 3).
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Figure 3. Inside look of how cancer spreads
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The central mechanism for spreading cells in complex tissues is the process called Epithelial- Mesenchymal Transdifferientiation (EMT)(Kyprianou, 2010). This process, though important in embryonic development, contributes to the rapid invasion of epithelial-derived tumors. It provides abnormal cells with migratory and invasive properties and prevents apoptosis which then initiates metastasis(Kalluri and Neilson, 2003). The major inducer for this process is a multifunctional cytokine protein called transforming growth factor-beta (TGF-β)(Wilis and Borok 2007).
The Discovery
The protein was discovered by Arindam Chaudhury, George S. Hussey, Partho S Ray, Ge Jin, Paul L. Fox, Philip H. Howe and explained fully in their journal entitled “TGF-[beta]-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI" published in Nature Cell Biology last February 2010. The project was brought about when the researchers began investigating what caused EMT, which as aredy known causes the releasing cancer cells from the surface of the original tumor and thus allowing it to start new tumors in other parts of the body by chaning the epithelial cells into mesencyhmal cells (Paddock 2010).
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Figure 4. Representation of Dab2
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In their research they examined the biochemistry behind the spreading of cancer in laboratory animals and found out that the disabled homolog 2 Dab2 protein caused metastasis (Figure 4). At present, Dab2 mRNA, as encoded by the Dab2 gene, is only known to be expressed in ovarian epithelial cells and absent in ovarian cancer cell. The researchers noted that TGF-beta triggered the formation of Dab2 which in turn activated EMT. They removed Dab2 from the equation and somehow EMT did not occur. The researchers then concluded that there exists a TGF-beta-inducible post-transcriptional regulon that controls EMT during the development and metastatic progression of tumors (Paddock, 2010).
The Future
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The researchers note that their discovery is a complicated cascade flow of events. The researchers remain optimistic that with further studies more information can be learned regarding the signalling pathway in modulating EMT. With this, it is hoped that someday drugs could be designed to delay or halt EMT and control tumor progression. The researchers further added that with this discovery, it may lead to the better understanding of the progression of other diseases as well. (Paddock, 2010)
- “Definition of Cancer”. MedicineNet.com. (2004 September 18) Retrieved October 1, 2010 from: http://www.medterms.com/script/main/art.asp?articlekey=2580
- Emer, D. “Top Ten Leading Causes of Mortality in the Philippines” (2010) Retrieved October 1, 2020 from: http://www.docstoc.com/docs/37270129/Top-Ten-Leading-Causes-of-Mortality-in-the-Philippines
- Ever, Jessica. “Overview: Stages of Cancer”. CentersiteLLC (2010) Retrieved September 27, 2010 from: http://www.mentalhelp.net/poc/view_doc.php?type=doc&id=5194
- Hill, Brian. “Stages of Cancer” Oral Cancer Foundation Inc.(2010) Retrieved October 1, 2010 from http://www.oralcancerfoundation.org/facts/stages_cancer.htm
- Kalluri, Raghu and Neilson, Eric. “Epithelial-Mesenchymal Transition and its Implications for Fibrosis”. American Society for Clinical Investigation (2003 December 15). Retrieved September 27, 2010 from: http://www.jci.org/articles/view/20530
- Kyprianou, Natasha. “ASK-ing EMT not to spread cancer”. National Academy of Sciences (2010) Retrieved September 29, 2010 from: http://www.pnas.org/content/107/7/2731.full
- Paddock, Catharine. “Protein That Triggers Cancer Spread Discovered”. Medical News Today (2010) Retrieved September 20, 2010 from: http://www.medicalnewstoday.com/articles/179151.php
- Smith, S.E, “What are the Different Stages of Cancer?”. Conjecture Corporation (2010 October 4) Retrieved September 27, 2010 from: http://www.wisegeek.com/what-are-the-different-stages-of-cancer.htm
- Willis, Bringham and Borok, Zea. “TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease”. American Physiological Society (2007) Retrieved September 29, 2010 from: http://ajplung.physiology.org/cgi/content/full/293/3/L525