THE RELATIONSHIP BETWEEN CHRONIC INFLAMMATION AND MALIGNANCY

INTRODUCTION:

Definition of terms:

Chronic inflammation is inflammation of prolonged duration (weeks or years) in which continuing inflammation, tissue injury, and healing, often by fibrosis, proceed simultaneously.

Characteristics of inflammation:

Chronic inflammation is characterized by a different set of reactions:

1.       Infiltration with mononuclear cells, including macrophages, lymphocytes, and plasma cells.

2.       Tissue destruction, largely induced by the products of the inflammatory cells.

3.       Repair, involving new vessel proliferation (angiogenesis) and fibrosis.

Malignancy can be defined as a tendency to progress in virulence. In popular usage, it is any condition that, if uncorrected, tends to worsen so as to cause serious illness or death. Cancer is the best known example.

Deregulated inflammatory response plays a pivotal role in the initiation, development and progression of tumours. Potential molecular mechanism(s) that drive the establishment of an inflammatory-tumour microenvironment is not entirely understood owing to the complex cross-talk between pro-inflammatory and tumorigenic mediators such as cytokines, chemokines, oncogenes, enzymes, transcription factors and immune cells.

Factors affecting activation and deactivation of molecular mediators:

These molecular mediators are critical linchpins between inflammation and cancer, and their activation and/or deactivation are influenced by;

      1. Extrinsic (i.e. environmental and lifestyle)

      2. Intrinsic (i.e. hereditary) factors.

At present, the research pertaining to inflammation-associated cancers is accumulating at an exponential rate. Interest stems from hope that new therapeutic strategies against molecular mediators can be identified to assist in cancer treatment and patient management.

In a sense, tumours act as wounds that fail to heal (2).The hallmarks of cancer-related inflammation include the presence of inflammatory cells and inflammatory mediators (for example, chemokines, cytokines and prostaglandins) in tumour tissues, tissue remodelling and angiogenesis (growth of new blood vessels) similar to that seen in chronic inflammatory responses, and tissue repair.
Other terms:

Cytokines: A small protein released by cells that has a specific effect on the interactions between cells, on communications between cells or on the behavior of cells. The cytokines includes the interleukins, lymphokines and cell signal molecules, such as tumor necrosis factor and the interferons, which trigger inflammation and respond to infections.

Chemokine: One of a large group of proteins that act as lures and were first found attracting white blood cells. The chemokines are involved in a wide variety of processes including acute and chronic types of inflammation, infectious diseases, and cancer. Chemokines may lure cancer cells and help determine the sites to which cancer cells spread by metastasis.

Prostaglandin: One of a number of hormone-like substances that participate in a wide range of body functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation. Prostaglandins are derived from a chemical called arachidonic acid.

An overview of inflammation and carcinogenesis

A key attribute of an effective Immune system is to be able to detect the presence of trouble - this could be dead or damaged cells, tumour cells or infection with viruses, bacteria or eukaryotic parasites. Some aspects of this have already been dealt with; acute inflammation is the major system for sensing trauma. However, the Immune system needs to be able to detect more subtle changes and also needs to encourage a two-way communication between the innate and adaptive immune responses.

In terms of protection against infection the ability of certain cells to detect the presence of prokaryotic molecules (like bacteria) is of primary importance. Though there is considerable sophistication and subtlety to the mechanisms which do this we can focus here on 3 cells types: mast, macrophages and dendritic cells.

Presence of LYVE-1-positive macrophages during bladder cancer progression. Representative photomicrographs indicating LYVE-1-positive cells. Tumour associated macrophages (TAMS) are indicated by a red arrow.

Evidence currently available suggests that in established, progressively growing solid tumours, tumour associated macrophages (TAMs) are reprogrammed to induce immune suppression of host defenses in situ, through release of specific cytokines, prostanoids and other humoral mediators. This disordered response, results in the inhibition of effective anti-cancer cell-mediated immune mechanisms. Concurrently, TAMs produce tumour growth promoting factors. The summation of this complex interplay of biological factors results in progressive tumour growth and tumour cell dissemination.

Conclusion:

A comprehensive knowledge of the relationship and interaction between chronic infection and malignancies gives a greater  insight into the pathogenesis of cancer and its underlying effects.

Referencing:

http://nutritionaloncology.org/cancerCells&Inflammation.html

http://medical-dictionary.thefreedictionary.com/Malignancy

https://www.linkedin.com/pulse/relationship-between-chronic-inflammation-cancer-emma-pettengale

Robins basic pathology, 9^th edition, chapter 2,  page 53