Inflammation and Carcinogenesis

doi:10.4236/jct.2013.410173

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Journal of Cancer Therapy, 2013, 4, 1449-1451

Published Online December 2013 (http://www.scirp.org/journal/jct)

http://dx.doi.org/10.4236/jct.2013.410173

Open Access JCT

1449

Inflammation and Carcinogenesis

Yu-Sheng Wu, Shiu-Nan Chen*

Department of Life Science, National Taiwan University, Taipei, Taiwan

Email: *[email protected]

Received November 6th, 2013; revised November 26th, 2013; accepted December 3rd, 2013

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

We consider that inflammatory substances play an important role in the carcinogenesis process. In the process, cyto-

kines and growth factor secreted by cells can actively recruit immune cells in the carcinogenesis microenvironment,

further, promote carcinogenesis progression. The carcinogenesis microenvironment even subverted the immune system,

moreover, enhanced the carcinogenesis through immune suppressive mechanisms within the carcinogenesis microen-

vironment.

Keywords: Inflammation; Carcinogenesis; Microenvironment

1. Introduction

Inflammation is known to be a crucial adaptive response

for animals, and the mechanism is a complex interaction

with molecular mediators even the functions of immune

cells in a microenvironment through a response that oc-

curs at all levels of biological organization [1]. In this

process, cooperation among cells and mediators occurs,

and a wide range of factors are involved in the classical

immune response, including 1) the stage of the inflam-

mation process; 2) the tissue or organ involved; and 3)

whether the inflammation is acute and resolving or

chronic and non-resolving [2]. The inflammation process

involves vascular permeability, active migration of blood

cells, and the passage of plasma constituents into injuri-

ous tissue [3]. Through the infiltration of immune cells,

studies have shown that the inflammation process plays a

crucial role in atherosclerosis [4]. Blood leukocytes, me-

diators of host defenses and inflammation, localize in the

earliest lesions of atherosclerosis in experimental animals.

The study of inflammation in atherosclerosis has afford-

ed considerable new insights into the mechanisms un-

derlying the recruitment of leukocytes [5]. Recently,

studies have indicated the role of inflammation in Alz-

heimer disease (AD) [6]. Inflammatory components re-

lated to AD neuroinflammation include brain cells, such

as microglia and astrocytes, the complement system, and

cytokines and chemokines [7]. Regarding cancer devel-

opment [8], pro-inflammatory cytokines, including inter-

leukin (IL)-1α, IL-1β, IL-6, IL-8, IL-18, chemokines,

matrix metallopeptidase (MMP)-9, and vascular endothe-

lial growth factor (VEGF) are primarily regulated by the

transcription factor nuclear factor (NF)-kB, which is ac-

tive in most tumors and is induced by carcinogens [9].

2. Mediators of Inflammation

Studies have investigated the cytokines involved in the

inflammation response by using various animal models.

The expression of pro-inflammatory cytokines, such as

tumor necrosis factor alpha (TNF)-α, is significantly in-

creased in the adipocytes of obese animals (ob/ob mouse,

db/db mouse, and fa/fa Zucker rat) [10]. The activation

of TNF-α might induce leukocytes express adhesion

molecules on the cell surface [11], leading to diapedesis

through indiv idual vascular endothelial cells [12]. IL-6 is

an adipokine [13] thought to be a mediator of anti-in-

flammation [14] that is produced by adipose tissue and

liver-resident macrophages that are activated in response

to hepatocyte death [15]. IL-6-deficient mice exhibit a

marked decrease in inflammatory response, granulation

tissue formation, and re-epithelialization [16]. The IL-1

family, which includes IL-1α and IL-1β, exhibits strong

pro-inflammatory activ ities an d plays a majo r role in ho st

responses to exogenous and endogenous noxious stimuli

*Corresponding a uthor.

Inflammation and Carcinogenesis

1450

[17]. IL 1 induces the expression of adhesion molecules

on endothelial cells and elicits stromal cells to release

chemokines that promote the recruitment of inflamma-

tory cells at the inflammation site [18]. Such inflamma-

tion occurs significantly in cases of comorbidity and

might contribute to the increased risk of developing car-

diovascular accidents observed in these patients [19].

IL-10, a cytokine with anti-inflammatory properties,

plays a central role in infection that involv es limiting the

immune response to pathogens and thereby preventing

damage to the host [20]. Recently, research has shown

that IL-10 and related cytokines can facilitate the tis-

sue-healing process in injuries caused by infection or

inflammation [21 ]. According to these stud ies, mediators

thought to be involved in the regulation of inflammation

responses such as leukocyte recruitment, adhesion mole-

cule expression, and wound healing in the late phase of

inflammation.

3. Inflammation and Cancer

The inflammatory cells and cytokines present in tumors

are more likely to contribute to tumor growth, progres-

sion, and immunosuppression than they are to induce an

effective host antitumor response [22]. Inflammatory

leukocytes such as neutrophils, monocytes, macrophages,

and eosinophils provide the soluble factors that are

thought to mediate the development of inflammation-

associated cancer, although other cells, including the

cancer cells, also participate [23]. In various forms of

inflammation, the tumor microenvironment contains in-

nate immune cells (including macrophages, neutrophils,

mast cells, myeloid-derived suppressor cells, dendritic

cells, and natural killer cells) and adaptive immune cells

(T and B lymphocytes) in addition to cancer cells and

their surrounding stroma (which consist of fibroblasts,

endothelial cells, pericytes, and mesenchymal cells) [24].

Previously published literature has indicated that the re-

sulting activity of inflammatory mediators, such as cyclo-

oxygenase (COX)-2, creates a tumor-promoting envi-

ronment in which transformed epithelial cells [25] and

COX-2 are inducible by oncogenes ras and scr, IL-1,

hypoxia, ultraviolet lig ht, epidermal growth factor, trans-

forming growth factor beta, and TNF-α [26]. Studies

have expanded on th e concept that inflammation is a cri-

tical component of tumor progression, and many cancers

arise from sites of infection, chronic irritation, and in-

flammation [27]. Investigation of the inflammatory sub-

stances involved in the process may help us prevent even

cure the cancer disease.

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Open Access JCT

Inflammation and Carcinogenesis

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