-
World Journal of Gastroenterology Aug 2014Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on... (Review)
Review
Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells (pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biology and the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.
Topics: Animals; Biomarkers, Tumor; Cell Communication; Cell Transformation, Neoplastic; Extracellular Matrix; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplastic Stem Cells; Neovascularization, Pathologic; Pancreatic Neoplasms; Pancreatic Stellate Cells; Prognosis; Signal Transduction; Stromal Cells; Tumor Escape; Tumor Microenvironment
PubMed: 25170206
DOI: 10.3748/wjg.v20.i32.11216 -
NMR in Biomedicine Oct 2019Because of the spatial and temporal heterogeneities of cancers, technologies to investigate cancer cells and the consequences of their interactions with abnormal... (Review)
Review
Because of the spatial and temporal heterogeneities of cancers, technologies to investigate cancer cells and the consequences of their interactions with abnormal physiological environments, such as hypoxia and acidic extracellular pH, with stromal cells, and with the extracellular matrix, under controlled conditions, are valuable to gain insights into the functioning of cancers. These insights can lead to an understanding of why cancers invade and metastasize, and identify effective treatment strategies. Here we have provided an overview of the applications of MRI/MRS/MRSI to investigate intact perfused cancer cells, their metabolism and invasion, and their interactions with stromal cells and the extracellular matrix.
Topics: Cell Communication; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Neoplasm Invasiveness; Neoplasms; Perfusion; Stromal Cells
PubMed: 30693605
DOI: 10.1002/nbm.4053 -
Clinical & Translational Oncology :... Feb 2023Metastasis is the leading cause of mortality related to cancer. In the course of metastasis, cancer cells detach from the primary tumor, enter the circulation,... (Review)
Review
Metastasis is the leading cause of mortality related to cancer. In the course of metastasis, cancer cells detach from the primary tumor, enter the circulation, extravasate at secondary sites, and colonize there. All of these steps are rate limiting and decrease the efficiency of metastasis. Prior to their arrival, tumor cells can modify the secondary sites. These favorable microenvironments increase the probability of successful dissemination and are referred to as pre-metastatic niches. Cancer cells use different mechanisms to induce and maintain these niches, among which immune cells play prominent roles. The immune system, including innate and adaptive, enhances recruitment, extravasation, and colonization of tumor cells at distant sites. In addition to immune cells, stromal cells can also contribute to forming pre-metastatic niches. This review summarizes the pro-metastatic responses conducted by immune cells and the assistance of stromal cells and endothelial cells in the induction of pre-metastatic niches.
Topics: Humans; Endothelial Cells; Neoplasms; Carcinogenesis; Stromal Cells; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 36136272
DOI: 10.1007/s12094-022-02950-4 -
The Surgical Clinics of North America Apr 2017Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The stomach is the most common site of origin. Management... (Review)
Review
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The stomach is the most common site of origin. Management of GISTs changed after the introduction of molecularly targeted therapies. Although the only potentially curative treatment of resectable primary GISTs is surgery, recurrence is common. Patients with primary GISTs at intermediate or high risk of recurrence should receive imatinib postoperatively. Imatinib is also first-line therapy for advanced disease. Cytoreductive surgery might be considered in advanced GIST for patients with stable/responding disease or limited focal progression on tyrosine kinase inhibitor therapy. GIST requires multidisciplinary management.
Topics: Antineoplastic Agents; Biological Products; Chemotherapy, Adjuvant; Combined Modality Therapy; Endoscopy, Gastrointestinal; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Molecular Targeted Therapy; Neoplasm Recurrence, Local
PubMed: 28325196
DOI: 10.1016/j.suc.2016.12.001 -
Future Oncology (London, England) May 2017For many cancer types, cancer cells invade into surrounding tissues by collective movement of cell groups that remain connected via cell-cell junctions. This migration... (Review)
Review
For many cancer types, cancer cells invade into surrounding tissues by collective movement of cell groups that remain connected via cell-cell junctions. This migration is completely distinguished from single-cell migration, in which cancer cells disrupt the tight intercellular junctions and gain a mesenchymal phenotype. Recently, emerging evidence has revealed that collective cell invasion depends on not only cell-intrinsic mechanisms but also on extracellular mechanisms by bidirectional interplay between the tumor cell and the tumor environment. Herein, in this review we discuss the role and underline mechanisms of tumor microenvironment in collective tumor cell invasion, particularly focusing on extracellular matrix remodeling and cross-talk between tumor and stromal cells.
Topics: Animals; Biophysical Phenomena; Cancer-Associated Fibroblasts; Cell Movement; Extracellular Matrix; Humans; Matrix Metalloproteinases; Neoplasm Invasiveness; Neoplasms; Proteolysis; Signal Transduction; Stromal Cells; Tumor Microenvironment
PubMed: 28075171
DOI: 10.2217/fon-2016-0501 -
Archives of Pharmacal Research Jan 2019Cancer is a systemic disease in which neoplastic cells interact with multiple types of non-neoplastic stromal cells as well as non-cellular components. The extracellular... (Review)
Review
Cancer is a systemic disease in which neoplastic cells interact with multiple types of non-neoplastic stromal cells as well as non-cellular components. The extracellular matrix (ECM) is a non-cellular component that is aberrantly regulated in many types of tumor microenvironments. Since the ECM generally maintains the tissue structure and provides mechanical forces in the tumor microenvironment, it has been simply assumed to act as a physical barrier for cancer metastasis and have a passive role in cancer progression. However, a substantial body of evidence has suggested that ECM remodeling influences many aspects of cancer cell behaviors and its importance has attracted attention in cancer biology. Abnormal ECM affects cancer progression through several ways such as inducing hypoxia, immune cells interaction by promoting mesenchymal shift and cell transformation. Accordingly, in this review we summarize and discusses the role of the ECM in modulating epithelial cells and surrounding stomatal cell components and considers its prospects in cancer biology.
Topics: Animals; Disease Progression; Extracellular Matrix; Humans; Immunity, Cellular; Neoplasm Invasiveness; Neoplasms; Tumor Microenvironment
PubMed: 30515725
DOI: 10.1007/s12272-018-1097-0 -
Cells Dec 2021The tumour microenvironment (TME) is now recognised as a hallmark of cancer, since tumour:stroma crosstalk supports the key steps of tumour growth and progression. The... (Review)
Review
The tumour microenvironment (TME) is now recognised as a hallmark of cancer, since tumour:stroma crosstalk supports the key steps of tumour growth and progression. The dynamic co-evolution of the tumour and stromal compartments may alter the surrounding microenvironment, including the composition in metabolites and signalling mediators. A growing number of evidence reports the involvement of the endocannabinoid system (ECS) in cancer. ECS is composed by a complex network of ligands, receptors, and enzymes, which act in synergy and contribute to several physiological but also pathological processes. Several in vitro and in vivo evidence show that ECS deregulation in cancer cells affects proliferation, migration, invasion, apoptosis, and metastatic potential. Although it is still an evolving research, recent experimental evidence also suggests that ECS can modulate the functional behaviour of several components of the TME, above all the immune cells, endothelial cells and stromal components. However, the role of ECS in the tumour:stroma interplay remains unclear and research in this area is particularly intriguing. This review aims to shed light on the latest relevant findings of the tumour response to ECS modulation, encouraging a more in-depth analysis in this field. Novel discoveries could be promising for novel anti-tumour approaches, targeting the microenvironmental components and the supportive tumour:stroma crosstalk, thereby hindering tumour development.
Topics: Apoptosis; Cell Movement; Cell Proliferation; Endocannabinoids; Endothelial Cells; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 34943903
DOI: 10.3390/cells10123396 -
Nature Genetics Apr 2015Recent molecular classifications of colorectal cancer (CRC) based on global gene expression profiles have defined subtypes displaying resistance to therapy and poor...
Recent molecular classifications of colorectal cancer (CRC) based on global gene expression profiles have defined subtypes displaying resistance to therapy and poor prognosis. Upon evaluation of these classification systems, we discovered that their predictive power arises from genes expressed by stromal cells rather than epithelial tumor cells. Bioinformatic and immunohistochemical analyses identify stromal markers that associate robustly with disease relapse across the various classifications. Functional studies indicate that cancer-associated fibroblasts (CAFs) increase the frequency of tumor-initiating cells, an effect that is dramatically enhanced by transforming growth factor (TGF)-β signaling. Likewise, we find that all poor-prognosis CRC subtypes share a gene program induced by TGF-β in tumor stromal cells. Using patient-derived tumor organoids and xenografts, we show that the use of TGF-β signaling inhibitors to block the cross-talk between cancer cells and the microenvironment halts disease progression.
Topics: Animals; Cluster Analysis; Colorectal Neoplasms; Fibroblasts; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; Mice; Mice, Nude; Microarray Analysis; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplastic Stem Cells; Prognosis; Stromal Cells; Transcriptome
PubMed: 25706628
DOI: 10.1038/ng.3225 -
Medicina Clinica Oct 2017There are several tumours associated with gastrointestinal stromal tumour (GIST), most of them without an apparent family relationship; only 5% of them occur within the... (Review)
Review
There are several tumours associated with gastrointestinal stromal tumour (GIST), most of them without an apparent family relationship; only 5% of them occur within the context of a family syndrome. In this article the corresponding literature about the former has been reviewed. A search in Pubmed was carried out, the methodology of which is described in detail in the body of the article. A total of 88 articles have been chosen for the review, next to the application of limits as well as a manual review. GIST patients have a twofold risk of developing a second tumour than the general population (4-33% of them develop a second neoplasm, either synchronic or metachronic). Most incident tumours associated with GIST are gastrointestinal and genitourinary tumours. In addition, patients with second tumours have a worse survival rate than those without second tumours.
Topics: Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Prognosis; Risk; Urogenital Neoplasms
PubMed: 28736068
DOI: 10.1016/j.medcli.2017.06.010 -
Korean Journal of Radiology 2017The management of gastrointestinal stromal tumors (GISTs) has evolved significantly in the last two decades due to better understanding of their biologic behavior as... (Review)
Review
The management of gastrointestinal stromal tumors (GISTs) has evolved significantly in the last two decades due to better understanding of their biologic behavior as well as development of molecular targeted therapies. GISTs with exon 11 mutation respond to imatinib whereas GISTs with exon 9 or succinate dehydrogenase subunit mutations do not. Risk stratification models have enabled stratifying GISTs according to risk of recurrence and choosing patients who may benefit from adjuvant therapy. Assessing response to targeted therapies in GIST using conventional response criteria has several potential pitfalls leading to search for alternate response criteria based on changes in tumor attenuation, volume, metabolic and functional parameters. Surveillance of patients with GIST in the adjuvant setting is important for timely detection of recurrences.
Topics: Antineoplastic Agents; Benzamides; Chemotherapy, Adjuvant; Combined Modality Therapy; Exons; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Mutation; Neoplasm Recurrence, Local; Pyrimidines; Succinate Dehydrogenase; Tomography, X-Ray Computed
PubMed: 28096720
DOI: 10.3348/kjr.2017.18.1.84