Inflammation is now understood to play a critical role in the development and progression of many types of cancer. Disruption of the normal role of prostaglandins, especially PGE2, in tissue growth and response to inflammation, is now considered to be among the hallmarks that distinguish cancerous from normal tissue. Others include: evasion of the normal apoptotic process that multicellular organisms use to control the number and quality of cells in a tissue; self-sufficiency in growth signals, i.e., dysfunction of nor mal signaling pathways that stimulate and restrain cell growth; unlimited potential for replication, a property shared with stem cells; sustained production of new from existing vascular tissue (angiogenesis); ability to invade other tissue and metastasize. These are some of the functional consequences of the unrepaired mutations that underlie the conversion of a normal cell to a cancerous one.

Signs of inflammation are present in many cancerous and precancerous tissues. Tumor growth is com plex and involves many different cell types, including associated noncancer cells and bone-marrow-derived cells which contribute to the growth and angiogenic capacity of cancer cells. Blocking the pro-inflammatory cytokines or other mediators from these cells can slow cancer progression. On the other hand, infiltration of the tumor site with lymphocytic cells can inhibit tumor growth, so inhibition of this process is counterproductive. Thus the effects of the mixture of eicosanoids to which tumor cells are exposed may be difficult to unravel and even more difficult to target therapeutically.

PGE2 is the most common and abundant prostaglandin found to be elevated, and associated with a poor prognosis, in tumors of the colon, breast, lung, and esophagus. From many studies of models of colon cancer it is clear that COX-2 is a major source of the elevated PGE2 levels, although in tumors in other tissues, COX-1 may also be involved. PGE2’s actions include inhibition of apoptosis, stimulation of proliferation, and angiogenesis; in addition it acts as an immunosuppressant and pro-inflammatory agent.

Cancer-causing agents that induce COX-2 in experimental settings include tobacco smoke, UV irradiation, growth factors, pro-inflammatory cytokines, and high levels of polyunsaturated fatty acids. Because of its role in tumorigenesis, the gene for COX-2 is considered an oncogene, that is a normal cellular gene that, when expressed in an unrestrained fashion, contributes to cancer. The role of COX-2 as a pivotal enzyme in PGE2 involvement in tumorigenesis is supported by many studies showing the efficacy of aspirin and other NSAIDs to act as chemopreventative agents in colon and gastrointestinal tract cancers, such as stomach and esophagus. A significant effort with regard to selective COX-2 inhibitors has been directed towards a more specific chemopreventative as well as therapeutic role in colorectal cancer, but problems remain with their use due to adverse cardiovascular effects (section III.D).

Not all prostaglandins are tumorigenic and not all tumors respond to NSAIDs as well as does colon cancer, suggesting that other elements of the prostaglandin pathway may also be involved. In fact, microsomal PGE synthase (mPGES-1) is overexpressed in several cancers including lung, breast, and colorectal and is currently under study as a cancer therapeutic target. In addition it has been recognized that high levels of PGE2 may be due not only to its production but also to reduction of its inactivation by 15-PGDH (section III.F). Markedly decreased levels of 15-PGDH mRNA have been seen in cancers of the bladder, colon, stomach, small intestine, lung, skin, kidney, pancreas, and liver. Although such a decrease in 15-PGDH in tumors is not universal, its frequent appearance suggests that reduced removal of PGE2 contributes to its elevation in a tumorigenic setting. From this standpoint, it is clear that in many situations, 15-PGDH may be considered a tumor suppressor.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم صناعة الشبابيك يواصل أعمال الإدامة لأحد أبواب حرم مرقد أبي الفضل العباس (عليه السلام)

ضمن فعاليات ملتقى النورين.. المجمع العلمي يقيم ندوة فكرية في بابل

المجمع العلمي يحيي ليلة القدر الأولى في مقام الإمام المهدي (عجّل الله فرجه)

مركز السيد جعفر الحلي الطبي يقدم الاستشارات والخدمات الصحية في ليالي القدر المباركة

المزيد

الآخبار الصحية

خمسة مؤشرات صحية مهملة قد تنقذ حياتك

متى تكون الحمى طبيعية؟

التدخين الإلكتروني يهدد قلبك.. دراسة جديدة تكشف مخاطر ارتفاع ضغط الدم

دراسة تكشف فائدة بعض أنواع الشاي في محاربة الاكتئاب

المزيد

الآخبار التكنلوجية

الجهاز المناعي يظهر دورا غير متوقع في صحة العظام

ابتكار من جامعة الشارقة منخفض التكلفة للحماية من الزلازل

اكتشاف تأثير غير متوقع للكاكاو على وظائف الدماغ

باحثون يرصدون أثر تغيّر المناخ في دم البشر

المزيد

مواضيع ذات صلة

Calcium and Phosphorus Homeostasis

Leukotrienes in Human Disease

Sanger Was the First to Determine the Sequence of a Polypeptide

The α-R Groups Determine the Properties of Amino Acids

Properties of the Functional Groups of Amino Acids

Examples of Biological Actions of Prostaglandins

Cyclooxygenase Inhibitors

Prostaglandin H Synthase/ Cyclooxygenase

Phospholipase A2

Overview of Eicosanoid Synthesis

Structure and Nomenclature of Eicosanoids

Water is an Excellent Nucleophile