A new measure for the malignancy of melanoma

March 12, 2009

Every tumor, starting from a size of a few millimeters, depends on a supply of nutrients and oxygen. Therefore, using special growth factors, it induces vascular wall cells of neighboring blood vessels to sprout new capillaries in order to get connected to the blood circulation.

This process called angiogenesis involves a number of different growth factors and their respective receptors on the vascular wall cells. The departments of Prof. Dr. Hellmut Augustin and Prof. Dirk Schadendorf of DKFZ and Mannheim Medical Faculty of the University of Heidelberg have investigated the role of a growth factor called angiopoietin-2 (Ang2) in malignant melanoma. The docking station of Ang2 is the receptor Tie2 on the surface of endothelial cells, which form the inner lining of blood vessels. Together with other signaling molecules, Ang2 induces sprouting of endothelial cells and the formation of new capillaries.

When measuring the Ang2 concentrations in blood samples of melanoma patients, the investigators discovered that larger tumors and more advanced disease stages correlate with high levels of Ang2. If one tracks the Ang2 levels of individual patients over time, a rise parallel to disease progression can be observed. In contrast, patients who have lived with the disease for a long time, i.e., whose disease is not or only slightly progressive, have lower Ang2 levels. The scientists found out that Ang2 concentration in blood serum is a more precise indicator of the progression and stage of the disease than previously used biomarkers.

This close association between melanoma progression and Ang2 level prompted the question of whether the Ang2 growth factor really only stimulates vascularization in the tumor or whether it has additional influence on the properties of the cancer cells themselves. Such an effect had not yet been proposed for any one of the various growth factors which act on the cells of the vascular walls. Melanoma cells were really found to produce both soluble Ang2 and the matching receptor, Tie2, on their own cell membrane. As a result, they are theoretically capable of activating themselves. In order to check this, researchers switched off the Ang2 production in melanoma cells using a genetic trick. Test systems in the culture dish subsequently revealed that the skin cancer cells had lost their ability to migrate. The migration tendency of cancer cells is regarded as important information about their ability to invade other tissue in the body and metastasize.

The tumor appears to seize the signaling system of vascularization and, thus, to strengthen its malignant properties. "Ang2 is a very promising candidate," Hellmut Augustin comments on the results, "�both as a biomarker for better monitoring of disease progression and as a target structure for therapy measures." Blocking Ang2 might not only attack the tumor's blood supply, but also reduce its malignant growth.

Helmholtz Association of German Research Centres

---

---

	Beating Melanoma: A Five-Step Survival Guide (A Johns Hopkins Press Health Book) by Steven Q. Wang (Author) Dr. Steven Q. Wang, a world-renowned skin cancer expert, provides an essential guide for people with melanoma and their families. The book’s unique, practical format approaches the disease in two phases, just as people with melanoma need to do. First comes a step-by-step guide for what Dr. Wang calls the "mad rush" phase—an intense and stressful period from diagnosis to completing initial treatment. Dr. Wang's calm guidance helps readers through this critical time, using an easy to understand plan for ensuring optimal treatment and survival outcomes. Once the mad rush phase is over, the "marathon phase" begins—life resumes its normal shape but with lingering concerns about new melanoma and metastases. Here Dr. Wang addresses common questions about prevention and prognosis. Beating...
	A Melanoma Patient's Survival Guide: Lemons Really Do Make Lemonade: You Just Have to Add a Little Sugar by Sally Welsh (Author) A Melanoma Patient’s Survival guide: Lemons Really Do Make Lemonade is an effort to bring awareness to the subject of melanoma. This insidious disease is being diagnosed in over 50,000 people a year in the United States alone. Melanoma will affect one in seventy-five people in California. That rate goes up each year. Melanoma can be a silent killer. This heart-warming book was written by a survivor of serious melanoma, Sally Welsh. Sally has shared her experience with thousands of people, and has prepared this book with the hope of making your journey a little easier. Her suggestions deal first of all with the questions you need to ask your doctor, before he cuts into you. You need to know about his initial scanning of you, whether he plans to use a “punch” biopsy or a “scrape”...
	Melanoma: Prevention, Detection, and Treatment; Second Edition (Yale University Press Health & Wellness) by Catherine M. Poole (Author), IV DuPont Guerry (Author) The incidence of melanoma has increased by 2000% since 1930, and one person dies each hour from the disease. This cutting-edge guide provides scientifically accurate information patients and their families need in order to understand melanoma and its treatment and to receive vital reassurance. It is also a resource for those who want information about preventing the disease or finding it early when it is most curable. Catherine M. Poole, a melanoma survivor and melanoma patient advocate for many national organizations, and Dr. DuPont Guerry, an internationally renowned melanoma expert, have collaborated to provide current, correct, and easily understood information on the disease. The authors have had first hand contact with a multitude of patients with melanoma, and they understand...
	What You Really Need to Know about Moles and Melanoma (A Johns Hopkins Press Health Book) by Jill R. Schofield (Author), William A. Robinson (Author) Throughout the world, the incidence of malignant melanoma is increasing at an alarming rate. This dramatic rise is largely due to more frequent and prolonged exposure to intense sun, the result of major changes in clothing styles, recreation, and lifestyle (including widespread access to midwinter resort vacations). Significantly, recent scientific studies have shown an increased number of moles on, and a higher rate of melanoma in, people with the greatest sunscreen use, pointing out the mistaken belief that using sunscreen means getting a "safe" tan. The truth is that most sunscreen provides protection from UVB rays—the rays that cause the sunburn you see and feel—but not from UVA rays—the cancer-causing rays that penetrate deeper into the skin.In this book, physicians Jill R....
	The Melanoma Book : A Complete Guide to Prevention and Treatment, Including the Early DetectionSelf-Exam Body Map by Howard L. Kaufman (Author) From the founder and Co-Director of the renowned Columbia University Melanoma Center, the first comprehensive guide to help you prevent—and survive—a diagnosis of melanoma. The fastest rising form of cancer worldwide, melanoma can strike at any age. Although rates of cure are higher than they used to be, experts often disagree about the best course of treatment and patients face a bewildering array of possibilities—often with precious little time to choose. Drawing on his years as one of the nation’s foremost researchers and specialists in the field of melanoma treatment, Dr. Howard L. Kaufman shares his easy- to-follow, whole-life plan for detecting melanoma early, making informed decisions after a diagnosis, and taking an active role in treatment.
	QuickFACTS Melanoma Skin Cancer: What You Need to Know-NOW by American Cancer Society (Author) This pocket-sized reference covers everything from the risk factors of melanoma skin cancer to the diagnosis procedure to living well after treatment. With greater public awareness, early detection of melanoma skin cancer is on the rise and mortality rates are declining; this medical guide emphasizes that all patients should be well-informed decision makers in planning their own treatment and is updated with the latest patient treatment guidelines. An advanced dictionary of cancer-related terms and a list of critical questions to ask health care administrators are also included.
	From Melanocytes to Melanoma: The Progression to Malignancy by Vincent J. Hearing (Editor), Stanley P. L. Leong (Editor) Leading researchers and clinicians join forces to explain how malignant melanoma develops from its benign precursor cell type. The authors focus on the molecular mechanisms involved in melanogenesis, in the malignant transformation of melanocytes, and in the further progression of primary melanomas into invasive and metastatic melanomas. They also review recent advances in our understanding of the basic biology of melanocytes and the development, migration, and differentiation of melanoblasts into melanocytes. The book provides an up-to-date understanding of the progressive mechanisms of oncological development in malignant melanoma, a likely model of malignant progress for other types of cancer, and the ongoing development of novel therapeutics.
	Unforeseen Consequences: A Physician's Personal Triumph Over Advanced Melanoma by Nicholas Steiner (Author) Dr. Nicholas Steiner is a Park Avenue internist in his mid-forties. He has a successful medical practice, a stable marriage with a home in the suburbs and enjoys good health. But when he develops melanoma, a potentially fatal type of cancer, everything ch
	Malignant Melanoma: Your Way Forward by Abaco Publishing You will never cure anything if you don’t do something about the underlying cause. This applies to every illness including malignant melanoma. In my book ‘Malignant Melanoma – Your way Forward’ I explain why it may have developed, giving you something to do to change the underlying causes and bring things under control. It could be related to a vaccination, being burned in the sun, associated with bad eating habits, a poor immune system, infections, too many antibiotics, toxic chemicals, geopathic stress and certainly stresses of everyday life affecting your emotions. When cancer declares itself, it could have been developing for ten or fifteen years. All of this is explained to you in detail as though you are with me in my consulting room. I then give ideas on how to change your...
	What You Need To Know About: Melanoma and Other Skin Cancers This booklet is for people diagnosed with the most common types of skin cancer like Melanoma, Basal cell skin cancer and Squamous cell skin cancer. Skin cancer is the most common type of cancer in the United States. Each year, more than 68,000 Americans are diagnosed with melanoma, and another 48,000 are diagnosed with an early form of the disease that involves only the top layer of skin. Also, more than 2 million people are treated for basal cell or squamous cell skin cancer each year. Basal cell skin cancer is several times more common than squamous cell skin cancer. Learning about medical care for skin cancer can help you take an active part in making choices about your care. This booklet tells about, diagnosis and staging, treatment, follow-up care, how to...