Inflammatory stress and sarcomagenesis: a vicious interplay

Abstract

Chronic inflammation represents one of the hallmarks of cancer, but its role in sarcomagenesis has long been overlooked. Sarcomas are a rare and heterogeneous group of tumors of mesenchymal origin accounting for less than 1 % of cancers in adults but 21 % of cancers in the pediatric population. Sarcomas are associated with bad prognosis, and their management requires a multidisciplinary team approach. Several lines of evidence indicate that inflammation has been implicated in sarcomagenesis leading to the activation of the key transcription factors HIF-1, NF- κB, and STAT-3 involved in a complex inflammatory network. In the past years, an increasing number of new targets have been identified in the treatment of sarcomas leading to the development of new drugs that aim to interrupt the vicious connection between inflammation and sarcomagenesis. This article makes a brief overview of preclinical and clinical evidence of the molecular pathways involved in the inflammatory stress response in sarcomagenesis and the most targeted therapies.

Role of nuclear factor-kappa B in feline injection site sarcoma

“…Activation of NF-κB has been implicated in sarcomagenesis in chronic inflammation in humans [9]. In the present study, we have demonstrated that the nuclear localized NF-κB was detected in 83.3% of FISS cases, suggesting that NF-κB might play a role in development of FISS.…”

“…In fact, the concept that chronic inflammation links to the development of neoplasia has been proposed in 1863 by Rudolf Virchow [9]. Numerous mediators in response to chronic inflammation, such as cytokines, chemokines, growth factors and reactive oxygen and nitrogen species, could initiate DNA mutations and then provoke tumorigenesis through expression of critical signaling pathways [10, 11].…”

“…Numerous mediators in response to chronic inflammation, such as cytokines, chemokines, growth factors and reactive oxygen and nitrogen species, could initiate DNA mutations and then provoke tumorigenesis through expression of critical signaling pathways [10, 11]. Transcription factors, including hypoxia-inducible factor 1 (HIF-1), signal transducer and activator of transcription 3 (STAT-3), and nuclear factor-kappa B (NF-κB), are involved in a malignant transforming network of great complexity [9, 12, 13].…”

Inhibition of polypyrimidine tract-binding protein 3 induces apoptosis and cell cycle arrest, and enhances the cytotoxicity of 5- fluorouracil in gastric cancer cells

“…Western blotting assays were performed as described in a previous study (Zheng et al , 2013). Primary antibodies used are listed as follows: anti-PTBP3 (sc-100845, Santa Cruz Biotechnology, Santa Cruz, CA, USA), anti-PARP-1 (GTX100573, GeneTex, Irvine, CA, USA), anti-cleaved caspase-3 (9664s, Cell Signaling Technology, Beverly, MA, USA), anti-cleaved caspase-9 (sc-22182, Santa Cruz Biotechnology), anti-PTB (12582-1-AP, Proteintech, Rosemont, IL, USA), anti-TYMS (15047-1-AP, Proteintech), anti-MRP1 (GTX116046, GeneTex), anti-MRP2 (7985-1, Epitomics, Burlingame, CA, USA), anti-p-gp (7719-1, Epitomics), anti-Akt (4691, Cell Signaling Technology), anti-p-Akt (4060, Cell Signaling Technology), and anti-HDAC6 (12834-1-AP, Proteintech).…”

Soft tissue sarcoma in the dog – part 1: a current review

“…The majority of STS have the latter characteristic, which may suggest there is no common mutational pathway for development. Tumour initiation and progression may be a random event, possibly exacerbated by the increased mutagenesis that can accompany localised areas of inflammation (Radons , ).…”