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Colorectal Cancer and Adjacent Normal Mucosa Differ in Apoptotic and Inflammatory Protein Expression

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

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 14044

Special Issue Editor

Dr. Paola Sena

E-Mail Website
Guest Editor
Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy
Interests: colorectal cancer; apoptosis; inflammation; ovarian cancer; hormonal disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Today, colorectal cancer is the fourth most common type of tumor all over the world. CRC is the result of interactions between environmental and genetic factors. Among the former, the presence of chronic inflammation (as in inflammatory bowel diseases) is considered particularly important. As far as carcinogenesis is concerned, it is widely accepted that tumorigenesis results from an imbalance between cell proliferation and cell death. It is also becoming clearer that in response to cellular stresses, cells may use multiple mechanisms that ultimately determine cell death or survival. The molecular mechanisms underlying the disturbances, hereditary or acquired, of the function of the immune system and of the apoptotic pathways that regulate protection, promotion or tolerance against neoplastic transformation are still debated. Moreover, the colorectal adenoma–carcinoma sequence has provided a paradigmatic framework for understanding successive somatic genetic changes and consequent clonal expansions that lead to cancer. However, an understanding of the earliest phases of colorectal neoplastic changes—which may occur in morphologically normal tissue—is comparatively limited, as for most cancer types.

Dr. Paola Sena
Guest Editor

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Keywords

  • Molecular changes 
  • Colorectal cancer 
  • Normal mucosa 
  • Apoptotic proteins 
  • Inflammatory mechanism 
  • Adenoma–carcinoma sequence 
  • Early diagnosis

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Published Papers (4 papers)

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Research

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12 pages, 1374 KiB  
Article
The Cytotoxic Effect of Isolated Cannabinoid Extracts on Polypoid Colorectal Tissue
by Dana Ben-Ami Shor, Ilan Hochman, Nathan Gluck, Oren Shibolet and Erez Scapa
Int. J. Mol. Sci. 2022, 23(19), 11366; https://doi.org/10.3390/ijms231911366 - 26 Sep 2022
Cited by 7 | Viewed by 4527
Abstract
Purified cannabinoids have been shown to prevent proliferation and induce apoptosis in colorectal carcinoma cell lines. To assess the cytotoxic effect of cannabinoid extracts and purified cannabinoids on both colorectal polyps and normal colonic cells, as well as their synergistic interaction. Various blends [...] Read more.
Purified cannabinoids have been shown to prevent proliferation and induce apoptosis in colorectal carcinoma cell lines. To assess the cytotoxic effect of cannabinoid extracts and purified cannabinoids on both colorectal polyps and normal colonic cells, as well as their synergistic interaction. Various blends were tested to identify the optimal synergistic effect. Methods: Biopsies from polyps and healthy colonic tissue were obtained from 22 patients undergoing colonic polypectomies. The toxicity of a variety of cannabinoid extracts and purified cannabinoids at different concentrations was evaluated. The synergistic effect of cannabinoids was calculated based on the cells’ survival. Isolated cannabinoids illustrated different toxic effects on the viability of cells derived from colorectal polyps. THC-d8 and THC-d9 were the most toxic and exhibited persistent toxicity in all the polyps tested. CBD was more toxic to polypoid cells in comparison to normal colonic cells at a concentration of 15 µM. The combinations of the cannabinoids CBDV, THCV, CBDVA, CBCA, and CBGA exhibited a synergistic inhibitory effect on the viability of cells derived from colon polyps of patients. Isolated cannabinoid compounds interacted synergistically against colonic polyps, and some also possessed a differential toxic effect on polyp and adjacent colonic tissue, suggesting possible future therapeutic value. Full article
(This article belongs to the Special Issue Colorectal Cancer and Adjacent Normal Mucosa Differ in Apoptotic and Inflammatory Protein Expression)
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14 pages, 1191 KiB  
Article
Expression of Autophagic and Inflammatory Markers in Normal Mucosa of Individuals with Colorectal Adenomas: A Cross Sectional Study among Italian Outpatients Undergoing Colonoscopy
by Paola Sena, Stefano Mancini, Monica Pedroni, Luca Reggiani Bonetti, Gianluca Carnevale and Luca Roncucci
Int. J. Mol. Sci. 2022, 23(9), 5211; https://doi.org/10.3390/ijms23095211 - 6 May 2022
Cited by 1 | Viewed by 1921
Abstract
Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer-related deaths in Western industrialized countries. Lifetime risk of colorectal cancer may reach 6% of the population living in developed countries. In the current era of [...] Read more.
Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer-related deaths in Western industrialized countries. Lifetime risk of colorectal cancer may reach 6% of the population living in developed countries. In the current era of personalized medicine, CRC is no longer considered as a single entity. In more recent years many studies have described the distinct differences in epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and outcome depending on the anatomical site. The aim of our study is to assess in a multidimensional model the association between metabolic status and inflammatory and autophagic changes in the normal colorectal mucosa classified as right-sided, left-sided and rectum, and the presence of adenomas. One hundred and sixteen patients undergoing colonoscopy were recruited and underwent a complete serum lipid profile, immunofluorescence analysis of colonic biopsies for MAPLC3 and myeloperoxidase expression, matched with clinical and anthropometric characteristics. Presence of adenomas correlated with cholesterol (total and LDL) levels, IL-6 levels, and MAPLC3 tissue expression, especially in the right colon. In conclusion, serum IL-6 amount and autophagic markers could be good predictors of the presence of colorectal adenomas. Full article
(This article belongs to the Special Issue Colorectal Cancer and Adjacent Normal Mucosa Differ in Apoptotic and Inflammatory Protein Expression)
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16 pages, 7553 KiB  
Article
Galanin Receptors (GalR1, GalR2, and GalR3) Expression in Colorectal Cancer Tissue and Correlations to the Overall Survival and Poor Prognosis of CRC Patients
by Jacek Kiezun, Janusz Godlewski, Bartlomiej E. Krazinski, Zygmunt Kozielec and Zbigniew Kmiec
Int. J. Mol. Sci. 2022, 23(7), 3735; https://doi.org/10.3390/ijms23073735 - 29 Mar 2022
Cited by 9 | Viewed by 2354
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer in women and the third in men. The postoperative pathomorphological evaluation of patients with CRC is extremely important for future therapeutic decisions. Although our previous studies demonstrated high galanin (GAL) presence within [...] Read more.
Colorectal cancer (CRC) is the second most common cause of cancer in women and the third in men. The postoperative pathomorphological evaluation of patients with CRC is extremely important for future therapeutic decisions. Although our previous studies demonstrated high galanin (GAL) presence within tumor tissue and an elevated concentration of GAL in the serum of CRC patients, to date, there is a lack of data regarding GAL receptor (GalR) protein expression in CRC cells. Therefore, the aim of this study was to evaluate the presence of all three types of GalRs (GalR1, GalR2 and GalR3) within epithelial cells of the human colon and CRC tissue with the use of the immunohistochemical method and to correlate the results with the clinical-pathological data. We found stronger immunoreactivity of GalR1 and GalR3 in CRC cells compared to epithelial cells of the unchanged mucosa of the large intestine. No differences in the GalR2 protein immunoreactivity between the studied tissues were noted. We also found that the increased immunoexpression of the GalR3 in CRC tissue correlated with the better prognosis and longer survival (p < 0.0079) of CRC patients (n = 55). The obtained results suggest that GalR3 may play the role of a prognostic factor for CRC patients. Based on data from the TCGA-COAD project deposited in the GDC Data Portal, we also found that GalR mRNA in cancer samples and the adjacent normal tissue did not correlate with immunoexpression of the GalR proteins in CRC cells and epithelial cells of the unchanged mucosa. Full article
(This article belongs to the Special Issue Colorectal Cancer and Adjacent Normal Mucosa Differ in Apoptotic and Inflammatory Protein Expression)
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Review

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27 pages, 2847 KiB  
Review
Epithelial to Mesenchymal Transition: A Challenging Playground for Translational Research. Current Models and Focus on TWIST1 Relevance and Gastrointestinal Cancers
by Luana Greco, Federica Rubbino, Alessandra Morelli, Federica Gaiani, Fabio Grizzi, Gian Luigi de’Angelis, Alberto Malesci and Luigi Laghi
Int. J. Mol. Sci. 2021, 22(21), 11469; https://doi.org/10.3390/ijms222111469 - 25 Oct 2021
Cited by 10 | Viewed by 4354
Abstract
Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within [...] Read more.
Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal-like ones. Along the transition, a full-blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed E⇔M states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI). Full article
(This article belongs to the Special Issue Colorectal Cancer and Adjacent Normal Mucosa Differ in Apoptotic and Inflammatory Protein Expression)
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