Morphological Characteristics of the Stroma in Malignat Epithelial Neoplasms with Short Review of Skin Squamous Cell Carcinoma

Abstract The stroma of the neoplasm is a highly complex structure built by: specialized mesenchymal cells typical for each tissue surroundings, cancer associated fibroblast/myofibroblast, congenital or acquired immune cells, vascular network with endothelial cells and pericytes, mastocytes, macrophages, leukocytes and adipocytes, all together incorporated in the extracellular matrix. Each neoplasm produces its own unique microenvironment where the tumor grows and modifies. Although most of the cells of the host in the stroma have compulsory tumor suppressor ability, the stroma is changing during the malignant process and it even promotes growth, invasion and metastasis. Genetic changes that occur during the development of the cancer, which are guided by the malignant cells lead to changes in the stroma of the host that will overtake it and adjust it to their own needs. In the early stages of the tumor development and invasion, the basal membrane is degraded and the stroma becomes active and contains an increased number of fibroblasts, inflammatory infiltrate and newly composed capillaries which come into direct contact with the tumor cells. These changes lead to cancer invasion.

Download Full-text

Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?

Molecular Cancer ◽

10.1186/s12943-021-01347-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Mark P. Ward ◽

Laura E. Kane ◽

Lucy A. Norris ◽

Bashir M. Mohamed ◽

Tanya Kelly ◽

...

Keyword(s):

Cancer Cells ◽

Immune Cells ◽

Immune Cell ◽

Circulatory System ◽

Morphological Characteristics ◽

Metastatic Potential ◽

Coagulation Cascade ◽

Molecular Profile ◽

Great Promise ◽

Liquid Biopsies

AbstractCancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid biopsies” to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.

Download Full-text

The Role of the TGF-β Coreceptor Endoglin in Cancer

The Scientific World JOURNAL ◽

10.1100/tsw.2010.230 ◽

2010 ◽

Vol 10 ◽

pp. 2367-2384 ◽

Cited By ~ 64

Author(s):

Eduardo Pérez-Gómez ◽

Gaelle del Castillo ◽

Juan Francisco Santibáñez ◽

Jose Miguel Lêpez-Novoa ◽

Carmelo Bernabéu ◽

...

Keyword(s):

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Tumor Development ◽

Experimental Models ◽

Type I ◽

Type Ii ◽

Invasion And Metastasis ◽

Promising Target ◽

Growth Factor Beta

Endoglin (CD105) is an auxiliary membrane receptor of transforming growth factor beta (TGF-β) that interacts with type I and type II TGF-β receptors and modulates TGF-β signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy. In addition, recent studies on human and experimental models of carcinogenesis point to an important tumor cell–autonomous role of endoglin by regulating proliferation, migration, invasion, and metastasis. These studies suggest that endoglin behaves as a suppressor of malignancy in experimental and human epithelial carcinogenesis, although it can also promote metastasis in other types of cancer. In this review, we evaluate the implication of endoglin in tumor development underlying studies developed in our laboratories in recent years.

Download Full-text

Characterization of Oral Squamous Cell Carcinoma Associated Inflammation: A Pilot Study

Frontiers in Oral Health ◽

10.3389/froh.2021.740469 ◽

2021 ◽

Vol 2 ◽

Author(s):

Catherine Laliberté ◽

Nicole Ng ◽

Denise Eymael ◽

Kevin Higgins ◽

Aiman Ali ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Immune Cells ◽

Tumor Development ◽

Tissue Analysis ◽

Fluorescent Immunohistochemistry ◽

Pro Inflammatory Cytokines

Background: Oral squamous cell carcinoma (OSCC) is a devastating disease that is usually associated with a dense associated inflammatory infiltrate. Characterizing tumor-associated inflammation is critical to understand the pathogenies of tumor development and progression.Methods: We have tested a protocol to analyze tissue and salivary immune cells and mediators of 37 patients with OSCC at different stages and compared to eight chronic periodontitis patients and 24 healthy controls. Tissue analysis was based on fluorescent immunohistochemistry (FIHC) and inflammatory mediators were analyzed using a Luminex-based 30-Plex panel. Immune cells were analyzed using multichannel flow cytometry including CD45, CD66b, CD3, CD4, CD8, CD25, CD56, CD68, CD138, PD-1, and PD-L1.Results: We show an increase in OSCC-associated inflammation characterized by increased pro-inflammatory cytokines including IL-6, IL-8, TNFα, and GMCSF and increased salivary immune cells.Conclusion: We described a new method to analyze salivary inflammatory markers that can be used in future studies to monitor disease progression and prognosis.

Download Full-text

Genetic Events Responsible for Colorectal Tumorigenesis: Achievements and Challenges

Tumori Journal ◽

10.1177/030089169307900401 ◽

1993 ◽

Vol 79 (4) ◽

pp. 235-243 ◽

Cited By ~ 7

Author(s):

Boris Kopnin

Keyword(s):

Tumor Suppressor ◽

Tumor Development ◽

Suppressor Gene ◽

Colorectal Carcinogenesis ◽

Genetic Changes ◽

Colorectal Tumorigenesis ◽

Ras Genes ◽

Carcinoma Cell Lines ◽

Kinase C ◽

Multistep Process

Colorectal carcinogenesis is a multistep process that is accompanied by accumulation of changes in proto-oncogenes and tumor-suppressor genes. APC/MCC, RAS, DCC, p53 mutations and/or allelic losses, hyperexpression of c-MYC and RB genes, as well as other genomic alterations appear at characteristic stages of tumor development and are observed in most neoplasms. However, consideration of each of these abnormalities leaves many unanswered questions. The striking data on recurrent amplification of the RB tumor-suppressor gene as well as suppressive activities of protein kinase C and activated RAS genes, at least in some colon carcinoma cell lines, suggest the unusual effects of some signalling pathways in colonic epithelial cells. The results obtained to date indicate that distinct sets of genetic changes may underlie the development of colorectal tumors.

Download Full-text

Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma

Carcinogenesis ◽

10.1093/carcin/bgz124 ◽

2019 ◽

Vol 41 (5) ◽

pp. 625-633 ◽

Cited By ~ 11

Author(s):

Beatrice M Razzo ◽

Nils Ludwig ◽

Chang-Sook Hong ◽

Priyanka Sharma ◽

Kellsye P Fabian ◽

...

Keyword(s):

Immune Cells ◽

Immune Cell ◽

Malignant Tumors ◽

Tumor Development ◽

Tumor Burden ◽

Cellular Reprogramming ◽

Cd8 T Lymphocytes ◽

Immune Cell Migration ◽

Phosphate Buffered Saline ◽

Hnscc Cell

Abstract Circulating tumor-derived exosomes (TEX) interact with a variety of cells in cancer-bearing hosts, leading to cellular reprogramming which promotes disease progression. To study TEX effects on the development of solid tumors, immunosuppressive exosomes carrying PD-L1 and FasL were isolated from supernatants of murine or human HNSCC cell lines. TEX were delivered (IV) to immunocompetent C57BL/6 mice bearing premalignant oral/esophageal lesions induced by the carcinogen, 4-nitroquinoline 1-oxide (4NQO). Progression of the premalignant oropharyngeal lesions to malignant tumors was monitored. A single TEX injection increased the number of developing tumors (6.2 versus 3.2 in control mice injected with phosphate-buffered saline; P < 0.0002) and overall tumor burden per mouse (P < 0.037). The numbers of CD4+ and CD8+ T lymphocytes infiltrating the developing tumors were coordinately reduced (P < 0.01) in mice injected with SCCVII-derived TEX relative to controls. Notably, TEX isolated from mouse or human tumors had similar effects on tumor development and immune cells. A single IV injection of TEX was sufficient to condition mice harboring premalignant OSCC lesions for accelerated tumor progression in concert with reduced immune cell migration to the tumor.

Download Full-text

Strategies to Interfere with Tumor Metabolism through the Interplay of Innate and Adaptive Immunity

Cells ◽

10.3390/cells8050445 ◽

2019 ◽

Vol 8 (5) ◽

pp. 445 ◽

Cited By ~ 11

Author(s):

Javier Mora ◽

Christina Mertens ◽

Julia K. Meier ◽

Dominik C. Fuhrmann ◽

Bernhard Brüne ◽

...

Keyword(s):

Tumor Growth ◽

Tumor Cells ◽

Immune Cells ◽

Tumor Development ◽

Metabolic Activation ◽

Growth And Survival ◽

Metabolic Characteristics ◽

Inflammatory Phenotype ◽

Tumor Outgrowth

The inflammatory tumor microenvironment is an important regulator of carcinogenesis. Tumor-infiltrating immune cells promote each step of tumor development, exerting crucial functions from initiation, early neovascularization, to metastasis. During tumor outgrowth, tumor-associated immune cells, including myeloid cells and lymphocytes, acquire a tumor-supportive, anti-inflammatory phenotype due to their interaction with tumor cells. Microenvironmental cues such as inflammation and hypoxia are mainly responsible for creating a tumor-supportive niche. Moreover, it is becoming apparent that the availability of iron within the tumor not only affects tumor growth and survival, but also the polarization of infiltrating immune cells. The interaction of tumor cells and infiltrating immune cells is multifaceted and complex, finally leading to different activation phenotypes of infiltrating immune cells regarding their functional heterogeneity and plasticity. In recent years, it was discovered that these phenotypes are mainly implicated in defining tumor outcome. Here, we discuss the role of the metabolic activation of both tumor cells and infiltrating immune cells in order to adapt their metabolism during tumor growth. Additionally, we address the role of iron availability and the hypoxic conditioning of the tumor with regard to tumor growth and we describe the relevance of therapeutic strategies to target such metabolic characteristics.

Download Full-text

The fermentation of polydextrose in the large intestine and its beneficial effects

Beneficial Microbes ◽

10.3920/bm2013.0065 ◽

2014 ◽

Vol 5 (3) ◽

pp. 305-313 ◽

Cited By ~ 19

Author(s):

H. Röytiö ◽

A.C. Ouwehand

Keyword(s):

Large Intestine ◽

Complex Structure ◽

Short Chain Fatty Acids ◽

Short Review ◽

Fermentation Products ◽

Beneficial Effects ◽

Glucose Polymer ◽

Upper Gastrointestinal

Polydextrose is a randomly bonded glucose polymer with a highly branched and complex structure. It resists digestion in the upper gastrointestinal tract and is partially fermented in the large intestine by the colonic microbes. Due to its complex structure, a plethora of microbes is required for the catabolism of polydextrose and this process occurs slowly. This gradual fermentation of polydextrose gives rise to moderate amounts of fermentation products, such as short chain fatty acids and gas. The production of these metabolites continues in the distal part of the colon, which is usually considered to be depleted of saccharolytic fermentation substrates. The fermentation of polydextrose modifies the composition of the microbiota in the colon, and has been shown to impact appetite and satiety in humans and improve the gastrointestinal function. The purpose of this short review is to summarise the in vitro, in vivo and human studies investigating the fermentation properties of polydextrose in the large intestine.

Download Full-text

Changing Patterns of Fungal Toxins in Crops: Challenges for Analysts

Journal of AOAC International ◽

10.5740/jaoacint.16-0110 ◽

2016 ◽

Vol 99 (4) ◽

pp. 837-841 ◽

Cited By ~ 7

Author(s):

J David Miller

Keyword(s):

New World ◽

Short Review ◽

Ear Rot ◽

Native Population ◽

Head Blight ◽

Cool Season ◽

Genetic Changes ◽

Cropping Patterns ◽

New Methods ◽

Changing Patterns

Abstract This short review discusses the need to manage climate-driven expansion of old toxins in new geographic areas (e.g., aflatoxin or fumonisin in corn in historically cooler areas, and ergot where rainfall and cropping patterns have changed). In addition, a renewed consideration of the toxins that can occur in feed sources used in cool-season dairy areas is needed (e.g., silage and distillers dry grains with solubles). A separate issue concerns genetic changes that are occurring in the species that cause Fusarium head blight/Gibberella ear rot. Small differences in climate appear to determine the distribution of the two dominant populations (native to the new world and from Asia). The chemotype that produces deoxynivalenol via the monoacetate at the 3 position results in the accumulation of somewhat more deoxynivalenol than the native population, which involves the monoacetate at the 15 position. There are also genetic changes occurring that have resulted in populations that produce different metabolites. Similarly, an increase in the area where Aspergillus flavus can thrive and the discovery of the sexual stage of this fungus have raised the potential of genetic change accelerated by climate. To address all these issues, new methods and increased availability of reference standards, as well as training and awareness, will be required.

Download Full-text

The Immune Endocannabinoid System of the Tumor Microenvironment

International Journal of Molecular Sciences ◽

10.3390/ijms21238929 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8929

Author(s):

Melanie Kienzl ◽

Julia Kargl ◽

Rudolf Schicho

Keyword(s):

Tumor Microenvironment ◽

Tumor Progression ◽

Immune Cells ◽

Cannabinoid Receptors ◽

Immune Cell ◽

Tumor Development ◽

Endocannabinoid System ◽

Cell Functions ◽

In Vitro Effects

Leukocytes are part of the tumor microenvironment (TME) and are critical determinants of tumor progression. Because of the immunoregulatory properties of cannabinoids, the endocannabinoid system (ECS) may have an important role in shaping the TME. Members of the ECS, an entity that consists of cannabinoid receptors, endocannabinoids and their synthesizing/degrading enzymes, have been associated with both tumor growth and rejection. Immune cells express cannabinoid receptors and produce endocannabinoids, thereby forming an “immune endocannabinoid system”. Although in vitro effects of exogenous cannabinoids on immune cells are well described, the role of the ECS in the TME, and hence in tumor development and immunotherapy, is still elusive. This review/opinion discusses the possibility that the “immune endocannabinoid system” can fundamentally influence tumor progression. The widespread influence of cannabinoids on immune cell functions makes the members of the ECS an interesting target that could support immunotherapy.

Download Full-text