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Systemic and Mucosal Inflammation in Colorectal Cancer: Underlying Factors, Significance, and Related Biomarkers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 15 May 2024 | Viewed by 7004

Special Issue Editor

Dr. Paola Sena

E-Mail Website
Guest Editor
Surgical, Medical, Dental, and Morphological Sciences Department with an Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Policlinico, Via Del Pozzo 71, I-41125 Modena, Italy
Interests: colorectal cancer; apoptosis; inflammation; ovarian cancer; hormonal disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the fourth most common tumor type in the world. Genetic and environmental factors contribute to the carcinogenesis of colorectal epithelial cells. It is widely accepted that the persistence of chronic inflammation, such as inflammatory bowel disease, is one of the most important environmental factors in the formation of CRC, and that unbalanced cell proliferation and cell death can lead to carcinogenesis. The function of the immune system and the genetic and acquired molecular mechanisms by which it regulates the phenotype or function or fate of tumor cells are still much debated. However, it is certain that multiple mechanisms are involved in cellular stress and determine cell survival and death. Although somatic genetic changes and subsequent clonal expansion and the polymeric framework leading to cancer can be provided by colorectal adenoma–carcinoma sequences, much controversy remains regarding changes that may occur in the early stages of CRC in morphologically normal tissues.

Dr. Paola Sena
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • molecular changes
  • colorectal cancer
  • normal mucosa
  • apoptotic proteins
  • inflammatory mechanism
  • adenoma–carcinoma sequence
  • cancer biomarkers

Published Papers (5 papers)

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Research

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15 pages, 3236 KiB  
Article
Berberine Improves Cancer-Derived Myocardial Impairment in Experimental Cachexia Models by Targeting High-Mobility Group Box-1
by Kei Goto, Rina Fujiwara-Tani, Shota Nukaga, Yoshihiro Miyagawa, Isao Kawahara, Ryoichi Nishida, Ayaka Ikemoto, Rika Sasaki, Ruiko Ogata, Shingo Kishi, Yi Luo, Kiyomu Fujii, Hitoshi Ohmori and Hiroki Kuniyasu
Int. J. Mol. Sci. 2024, 25(9), 4735; https://doi.org/10.3390/ijms25094735 - 26 Apr 2024
Viewed by 317
Abstract
Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat [...] Read more.
Cardiac disorders in cancer patients pose significant challenges to disease prognosis. While it has been established that these disorders are linked to cancer cells, the precise underlying mechanisms remain elusive. In this study, we investigated the impact of cancerous ascites from the rat colonic carcinoma cell line RCN9 on H9c2 cardiomyoblast cells. We found that the ascites reduced mitochondrial volume, increased oxidative stress, and decreased membrane potential in the cardiomyoblast cells, leading to apoptosis and autophagy. Although the ascites fluid contained a substantial amount of high-mobility group box-1 (HMGB1), we observed that neutralizing HMGB1 with a specific antibody mitigated the damage inflicted on myocardial cells. Our mechanistic investigations revealed that HMGB1 activated both nuclear factor κB and phosphoinositide 3-kinases-AKT signals through HMGB1 receptors, namely the receptor for advanced glycation end products and toll-like receptor-4, thereby promoting apoptosis and autophagy. In contrast, treatment with berberine (BBR) induced the expression of miR-181c-5p and miR-340-5p while suppressing HMGB1 expression in RCN9 cells. Furthermore, BBR reduced HMGB1 receptor expression in cardiomyocytes, consequently mitigating HMGB1-induced damage. We validated the myocardial protective effects of BBR in a cachectic rat model. These findings underscore the strong association between HMGB1 and cancer cachexia, highlighting BBR as a promising therapeutic agent for myocardial protection through HMGB1 suppression and modulation of the signaling system. Full article
(This article belongs to the Special Issue Systemic and Mucosal Inflammation in Colorectal Cancer: Underlying Factors, Significance, and Related Biomarkers)
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20 pages, 5411 KiB  
Article
Cellular Responses to Extracellular Vesicles as Potential Markers of Colorectal Cancer Progression
by Sonia Guarnerio, Robert Tempest, Rawan Maani, Stuart Hunt, Laura M. Cole, Christine L. Le Maitre, Keith Chapple and Nicholas Peake
Int. J. Mol. Sci. 2023, 24(23), 16755; https://doi.org/10.3390/ijms242316755 - 25 Nov 2023
Viewed by 1024
Abstract
The development of novel screening tests aims to support early asymptomatic diagnosis and subtyping patients according to similar traits in the heterogeneous cancer cohort. Extracellular vesicles (EVs) are promising candidates for the detection of disease markers from bodily fluids, but limitations in the [...] Read more.
The development of novel screening tests aims to support early asymptomatic diagnosis and subtyping patients according to similar traits in the heterogeneous cancer cohort. Extracellular vesicles (EVs) are promising candidates for the detection of disease markers from bodily fluids, but limitations in the standardisation of isolation methods and the intrinsic EV heterogeneity obtained from liquid biopsies are currently obstacles to clinical adoption. Here, cellular responses to cancer EVs were initially explored as potential complementary biomarkers for stage separation using colorectal cancer (CRC) SW480 and SW620 cell line models. A pilot study on a small cohort of CRC patients and controls was then developed by performing a multivariate analysis of cellular responses to plasma-derived EVs. Several cell activities and markers involved in tumour microenvironment pathways were influenced by the treatment of cell line EVs in a stage-dependent manner. The multivariate analysis combining plasma EV markers and cellular responses to plasma EVs was able to separate patients according to disease stage. This preliminary study offers the potential of considering cellular responses to EVs in combination with EV biomarkers in the development of screening methods. Full article
(This article belongs to the Special Issue Systemic and Mucosal Inflammation in Colorectal Cancer: Underlying Factors, Significance, and Related Biomarkers)
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14 pages, 2063 KiB  
Article
Immunometabolic Profile Associated with Progressive Damage of the Intestinal Mucosa in Adults Screened for Colorectal Cancer: Association with Diet
by Celestino González, Sergio Ruiz-Saavedra, María Gómez-Martín, Aida Zapico, Patricia López-Suarez, Ana Suárez, Adolfo Suárez González, Carmen González del Rey, Elena Díaz, Ana Alonso, Clara G. de los Reyes-Gavilán and Sonia González
Int. J. Mol. Sci. 2023, 24(22), 16451; https://doi.org/10.3390/ijms242216451 - 17 Nov 2023
Viewed by 1508
Abstract
Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it [...] Read more.
Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameters are altered in each phase of CRC development. In this work, we aimed to study the potential relationships of immunological and metabolic parameters with diet in a CRC-related lesion context. Dietary information was obtained using an annual semi-quantitative food-frequency questionnaire (FFQ) from 93 volunteers classified via colonoscopy examination according to the presence of intestinal polyps or adenocarcinoma. Cytokines, chemokines, and adipokines were determined from serum samples. We observed a reduction in adiponectin according to the damage to the mucosa, accompanied by an increase and decrease in C-X-C motif chemokine ligand 10 (CXCL10) and resistin, respectively, in CRC cases. The presence of aberrant crypt foci (ACF) in the polyp group was associated with higher tumor necrosis factor-alpha (TNF-α) concentrations. Vegetables were directly correlated with adiponectin and resistin levels, while the opposite occurred with red meat. A bioactive compound, soluble pectin, showed a negative association with TNF-α. Future dietary strategies could be developed to modulate specific immunological parameters in the context of CRC. Full article
(This article belongs to the Special Issue Systemic and Mucosal Inflammation in Colorectal Cancer: Underlying Factors, Significance, and Related Biomarkers)
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13 pages, 3435 KiB  
Article
HP1γ Prevents Activation of the cGAS/STING Pathway by Preserving Nuclear Envelope and Genomic Integrity in Colon Adenocarcinoma Cells
by Jorge Mata-Garrido, Laura Frizzi, Thien Nguyen, Xiangyan He, Yunhua Chang-Marchand, Yao Xiang, Caroline Reisacher, Iñigo Casafont and Laurence Arbibe
Int. J. Mol. Sci. 2023, 24(8), 7347; https://doi.org/10.3390/ijms24087347 - 16 Apr 2023
Cited by 1 | Viewed by 1569
Abstract
Chronic inflammatory processes in the intestine result in serious conditions such as inflammatory bowel disease (IBD) and cancer. An increased detection of cytoplasmic DNA sensors has been reported in the IBD colon mucosa, suggesting their contribution in mucosal inflammation. Yet, the mechanisms altering [...] Read more.
Chronic inflammatory processes in the intestine result in serious conditions such as inflammatory bowel disease (IBD) and cancer. An increased detection of cytoplasmic DNA sensors has been reported in the IBD colon mucosa, suggesting their contribution in mucosal inflammation. Yet, the mechanisms altering DNA homeostasis and triggering the activation of DNA sensors remain poorly understood. In this study, we show that the epigenetic regulator HP1γ plays a role in preserving nuclear envelope and genomic integrity in enterocytic cells, thereby protecting against the presence of cytoplasmic DNA. Accordingly, HP1 loss of function led to the increased detection of cGAS/STING, a cytoplasmic DNA sensor that triggers inflammation. Thus, in addition to its role as a transcriptional silencer, HP1γ may also exert anti-inflammatory properties by preventing the activation of the endogenous cytoplasmic DNA response in the gut epithelium. Full article
(This article belongs to the Special Issue Systemic and Mucosal Inflammation in Colorectal Cancer: Underlying Factors, Significance, and Related Biomarkers)
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20 pages, 3307 KiB  
Review
Different Roles of Apoptosis and Autophagy in the Development of Human Colorectal Cancer
by Giulia Orlandi, Luca Roncucci, Gianluca Carnevale and Paola Sena
Int. J. Mol. Sci. 2023, 24(12), 10201; https://doi.org/10.3390/ijms241210201 - 15 Jun 2023
Cited by 4 | Viewed by 1741
Abstract
Colorectal cancer (CRC) remains a major life-threatening malignancy, despite numerous therapeutic and screening attempts. Apoptosis and autophagy are two processes that share common signaling pathways, are linked by functional relationships and have similar protein components. During the development of cancer, the two processes [...] Read more.
Colorectal cancer (CRC) remains a major life-threatening malignancy, despite numerous therapeutic and screening attempts. Apoptosis and autophagy are two processes that share common signaling pathways, are linked by functional relationships and have similar protein components. During the development of cancer, the two processes can trigger simultaneously in the same cell, causing, in some cases, an inhibition of autophagy by apoptosis or apoptosis by autophagy. Malignant cells that have accumulated genetic alterations can take advantage of any alterations in the apoptotic process and as a result, progress easily in the cancerous transformation. Autophagy often plays a suppressive role during the initial stages of carcinogenicity, while in the later stages of cancer development it can play a promoting role. It is extremely important to determine the regulation of this duality of autophagy in the development of CRC and to identify the molecules involved, as well as the signals and the mechanisms behind it. All the reported experimental results indicate that, while the antagonistic effects of autophagy and apoptosis occur in an adverse environment characterized by deprivation of oxygen and nutrients, leading to the formation and development of CRC, the effects of promotion and collaboration usually involve an auxiliary role of autophagy compared to apoptosis. In this review, we elucidate the different roles of autophagy and apoptosis in human CRC development. Full article
(This article belongs to the Special Issue Systemic and Mucosal Inflammation in Colorectal Cancer: Underlying Factors, Significance, and Related Biomarkers)
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