Background: The histopathological structure of malignant tumours involves two essential compartments - the tumour parenchyma with the actual transformed cells, and the supportive tumour stroma. The latter consists of specialized mesenchymal cells, such as fibroblasts, macrophages, lymphocytes and vascular cells, as well as of their secreted products, including components of the extracellular matrix, matrix modifying enzymes and numerous regulatory growth factors and cytokines. In consequence, the tumour stroma has the ability to influence virtually all aspects of tumour development and progression, including therapeutic response.
Aim: In this article we review the current knowledge of tumor stroma interactions in urothelial carcinoma and present various experimental systems that are currently in use to unravel the biological basis of these heterotypic cell interactions.
Results: For urothelial carcinoma, an extensive tumour stroma is quite typical and markers of activated fibroblasts correlate significantly with clinical parameters of advanced disease. Another clinically important variable is provided by the stromal expression of syndecan-1.
Conclusion: Integration of markers of activated stroma into clinical risk evaluation could aid to better stratification of urothelial bladder carcinoma patients. Elucidation of biological mechanisms underlying tumour-stroma interactions could provide new therapeutical targets.
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http://dx.doi.org/10.1007/s00120-014-3754-3 | DOI Listing |
Virchows Arch
January 2025
Department of Pathology, Unidade Local de Saúde São João, Porto, Portugal.
This case report describes a rare case of bi-phenotypic gastric cancer with two distinct, but clonally related, histological components. The first component, associated with Epstein-Barr virus (EBV) infection, exhibited the morphological features of gastric carcinoma with lymphoid stroma, suggesting that EBV, as an effective immunogenic factor, may trigger a prominent immune response within the tumour microenvironment. The second component, which was EBV-negative, displayed tubular/papillary morphology and features of increased biological aggressiveness, such as high-grade areas and lymphatic invasion.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
January 2025
Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.
The recent uncovering of fibroblast heterogeneity has given great insight into the versatility of the stroma. Among other cellular processes, fibroblasts are now thought to contribute to the coordination of immune responses in a range of chronic inflammatory diseases and cancer. While the pathologic roles of myofibroblasts, inflammatory fibroblasts and cancer associated fibroblasts in disease are reasonably well understood, the mechanisms behind their activation remain to be uncovered.
View Article and Find Full Text PDFGenes Chromosomes Cancer
January 2025
Department of Pathology, NYU Grossman School of Medicine, New York, New York, USA.
Gene fusions involving JAZF1 are a recurrent event in low grade endometrial stromal sarcoma, and have been more recently described in few instances of endometrial stromal sarcoma-like tumors in the genitourinary tract of men. In this article, we describe a previously unreported spindle cell sarcoma harboring an in-frame JAZF1::NUDT5 gene fusion, arising in the chest wall of a 51-year-old man. The tumor had unique morphologic features resembling both endometrial stromal sarcoma and endometrial stromal sarcoma-like tumors, consisting of a mixture of cytologically bland and pleomorphic spindle cells with brisk mitotic activity, within an alternating myxoid and fibrous stroma.
View Article and Find Full Text PDFBio Protoc
January 2025
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Recurrent hormone receptor-positive (HR+) breast cancer is a leading cause of cancer mortality in women. Recurrence and resistance to targeted therapies have been difficult to study due to the long clinical course of the disease, the complex nature of resistance, and the lack of clinically relevant model systems. Existing models are limited to a few HR+ cell lines, organoid models, and patient-derived xenograft models, all lacking components of the human tumor microenvironment.
View Article and Find Full Text PDFCell Commun Signal
January 2025
School of Pharmacy, Naval Medical University, Shanghai, 200433, China.
Background: Cancer-associated fibroblasts (CAFs) are key components of the pancreatic adenocarcinoma (PAAD) tumor microenvironment (TME), where they promote tumor progression and metastasis through immunosuppressive functions. Although significant progress has been made in understanding the crosstalk between cancer cells and CAFs, many underlying mechanisms remain unclear. Recent studies have highlighted the importance of calcium signaling in enhancing interactions between tumor cells and the surrounding stroma, with the S100 family of proteins serving as important regulators.
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