Inflammation as Cause for Scar Cancers of the Lung

Abstract

The molecular and cellular basis of inflammation has become a topic of great interest of late because of the association between mechanisms of inflammation and risk for cancer. Inflammatory-mediated events, such as the production of reactive oxygen species (ROS), the activation of growth factors (for wound repair), and the altering of signaltransduction processes to activate cell-proliferation (to replace necrotic/apoptotic tissue cells), events that also can occur independently of inflammation, are all considered to be components of risk for a variety of cancers. Using scar cancer of the lung as an example, mechanisms of inflammation associated with recurring infections with Mycobacterium tuberculosis are discussed in the context that they may, in fact, be the major or sole cause of a cancer. Production of ROS, prostaglandins, leukotrienes, and cytokines in pulmonary tissues is greatly enhanced due to a cell-mediated immune response against macrophages infected with M. tuberculosis. These responses lead to the extensive fibrosis associated with recurring infections, possibly leading to decreased clearance of lymph and lymph-associated particles from the infected region. They also will enhance rates of cell division by inhibiting synthesis of P21, leading to enhanced progression from G0 arrest to G1 phase, from G1 to S phase, and from G2 to M phase of the cell cycle. By increasing rates of oxidative DNA damage and inhibiting apoptosis by enhancing synthesis of BCL-2, mutagenesis of progeny cells is enhanced, and these effects coupled with enhanced angiogenesis stimulated by COX-2 products lead to an environment that is highly conducive to tumorigenesis. Based on the evidence, it appears that but for an inflammatory response to recurring infections, some cases of scar cancer would not exist. By making appropriate lifestyle and dietary changes, a variety of anti-inflammatory effects can be produced, which should attenuate inflammation-induced risk for cancer.

Subtypes of White Blood Cells in Patients with Prostate Cancer or Benign Prostatic Hyperplasia and Healthy Individuals

“…It has been also reported that chronic inflammation is responsible for malignant tumors of epithelial origin including gastric, hepatic, colon, lung, pancreatic, esophageal, bladder and gallbladder cancer (Ardies, 2003;Wislez et al, 2003;Margolis et al, 2007). Despite unknown underlying mechanism, it has been suggested that toxic granules in neutrophils lead to inflammation of the neoplastic tissues, activating monocytes (Coussens and Werb, 2002;Nathan, 2006;Fridlender and Albelda, 2012).…”

“…Increased WBC count due to chronic inflammation is responsible for the development and progression of malignant tumors of epithelial origin including lung, breast, colon, hepatic, thyroid, prostate, gastric, bladder, intestine, and esophageal cancer. (Ardies, 2003;Wislez et al, 2003;Mantovani et al, 2004;Walsh et al, 2005;Margolis et al, 2007;Goswami et al, 2008;). Margolis et al (2007) reported increased neutrophil, monocyte and mean leukocyte count in patients with endometrial cancer compared to healthy controls.…”

Lung carcinogenesis induced by chronic tuberculosis infection: the experimental model and genetic control

“…This possibility is indirectly supported by observations of the so-called 'scar carcinomas' (Cagle et al, 1985). Ardies postulated that in many cases lung scarring occurred as a result of spontaneous healing after recurrent TB infection, and by triggering cycles of inflammatory and tissue repair processes generated a favorable environment for tumorigenesis (Ardies, 2003). On the other hand, lung cancer may develop autonomously and then provoke reactivation of latent TB by weakening local immunity.…”

Cancer pulmonaire

“…Dans les poumons, l'inflammation chronique peut être provoquée par des infections virales ou bactériennes répé-tées, par une exposition prolongée à des agents toxiques tels que le tabac ou l'amiante, ou être liée à des maladies respiratoires chroniques. Cette inflammation chronique pulmonaire peut augmenter le risque de carcinogenèse [2,3]. Une des molécules clés de l'inflammation est le facteur de transcription NF-B, dont la fonction dans le développement tumoral dans un contexte d'inflammation chronique a été démontrée [4,5].…”