Tubulin Expression in Melanocytic Skin Tumors
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The microtubulus system as a part of the cellular cytoskeleton contributes to cell movement. Microtubulus assembly and disassembly is considered to be essential for tumor invasion and serves as a target for tumor chemotherapy. Using immunohistochemical methods, we investigated the distribution of tubulin in normal skin and 34 melanocytic skin tumors. In normal skin, tubulin was strongly expressed in dermal nerves, melanocytes, fibroblasts within the papillary dermis and in myoepithelial cells. In melanocytic skin tumors, nevus cells and melanoma cells stained positive, particularly at the periphery of the lesions, where there were single cells and small nests. The main difference between benign and malignant melanocytic tumors was found in the stromal cells: In melanocytic nevi, the stromal fibroblasts were entirely tubulin negative; whereas, adjacent to the invasive edge in primary and metastatic malignant melanoma, the stroma fibroblasts were strongly positive. Our results show that tubulin is regularly expressed in melanocytic skin tumors and may serve as a prerequisite for cell movement. The pronounced expression of tubulin in fibroblasts surrounding malignant melanocytic skin lesions reflects a stromal alteration that might contribute to tumor invasion.Parenchyma
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Cancer associated stroma (CAS) consists mainly of a cellular fraction comprising fibroblasts, myofibroblasts, inflammatory cells, immune cells, endothelial cells, adipocytes and extracellular matrix (ECM). Recent reports have shown that the cancer stroma including the cellular fraction and ECM undergo considerable reprogramming during the process of tumourigenesis. Though there are some studies on CAS of human breast cancers (HBCs), similar studies are very much limited in canine mammary tumours. Hence, the present study was undertaken to classify the stromal types associated with malignant canine mammary tumours(CMTs). The excisional biopsy samples from 50 numbers of CMTs presented to Kerala Veterinary and Animal Sciences University hospitals at Mannuthy and Kokkalai during the period from November 2019 to December 2021 formed the study material. Histopathological stratification of cancer stroma was done using qualitative evaluation based on the stromal characteristics suggested for HBCs. Accordingly the cancer associated stroma in different tumour samples were classified as fibrotic stroma, inflammatory stroma and mixed stroma. Fibrotic stroma was further classified as mature/ sclerotic, intermediate and immature/desmoplastic types. The grade of tumours in relation to the type of stroma was also analysed and it was identified that with the exception of sclerotic stroma, all other stromal types could be observed in higher grades of CMTs. Desmoplastic and inflammatory stroma were predominantly seen associated with Grade II and Grade III tumours.
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Myofibroblast
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Pancreatic cancer is characterized by a dense stromal response. The stroma includes a heterogeneous mass of cells, including pancreatic stellate cells, fibroblasts, immune cells and nerve cells, as well as extracellular matrix proteins, cytokines and growth factors, which interact with the tumor cells. Previous research has indicated that stromal elements contribute to tumor growth and aggressiveness. However, recent studies suggest that some elements of the stroma may actually restrain the tumor. This review focuses on the complex interactions between the stromal microenvironment and tumor cells, discussing molecular mechanisms and potential future diagnostic and therapeutic approaches by targeting the stroma.
Hepatic stellate cell
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Carcinomas are composed of parenchymal and stromal elements, and the malignant behavior is principally dictated by the cancer cells. However, the malignant tumors not merely grow into a preexisting interstitial tissue, but they actively form a new stroma and modify their composition. Thus, the tumor stroma is significantly different from that of the neighboring tissues. Cancer cells may alter their stroma by cell-to-cell contact, soluble factors or by modification of the extracellular matrix (ECM), they induce myofibroblast differentiation and govern the desmoplastic stroma reaction. On the other hand, the stromal cells (especially the myofibroblasts) are able to modify the phenotype, invasiveness, metastatic capacity of carcinomas, typically promoting the progression. Regarding pancreatic cancer, the pancreatic stellate cells (PSCs) seem to be the key elements in the cross-talk between the parenchymal cells and the desmoplastic stroma. The tumor stroma is also rich in tumorassociated macrophages (TAM), but their role in the malignant process is contradictory and may be different in various tumor types, but most studies suggest a negative impact on the tumor growth. The relationship between the parenchymal and stromal elements is highly complex, they mutually alter their characteristics. Because the neostroma of the carcinomas largely seems to promote the invasiveness of the malignant tumors, novel therapeutic strategies are being evaluated targeting the stromal elements, with some encouraging, but still fragmentary results. Keywords: Tumor-stroma relationship, desmoplastic reaction, pancreatic stellate cells, review
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The role of tumor stroma in progression to malignancy has become the subject of intense experimental and clinical interest. The stromal compartment of organs is composed of all the non-epithelial cell types and maintains the proper architecture and nutrient levels required for epithelial and, ultimately, organ function. The composition of the reactive stroma surrounding tumors is vastly different from normal stromal tissue. Stromal phenotype can be correlated with, and predictive of, disease recurrence. In addition, the stroma is now seen as a legitimate target for therapeutic intervention. Although much has been learned about the role of the stromal compartment in development and disease in recent years, a number of key questions remain. Here we review how some of these questions are beginning to be addressed using new models of stromal-epithelial interaction.
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Cell reaction of the stroma of breast tumors is an indicator of the activity of the immunocompetent system in oncological patients. In this work, the cellular response of the tumor stroma was assessed histologically and morphometrically, including calculation of the number of cells-lymphocytes and plasmocytes in the centre of tumor and distally. The intensity of infiltration was estimated quantitatively depending on the type of tumor, patient's age, the presence or absence of regional metastases; moreover the effect of preoperative telegamma-therapy on the tumor stroma was taken into account. The data obtained indicated that the reaction of immunocompetent stromal cells depend on the type of tumor: it is maximum in the stroma of solid tumors and is less pronounced in the stroma of adenocarcinoma and scirrh, and it is minimum in mastopathy. Preoperative irradiation produced no significant reduction in the number of stromal cells. Patient's age rendered no effect on the intensity of cell reactions. The presence of tumor metastases in regional lymph nodes contributed to a fall in the number of stromal cells of solid tumors.
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Mammary stromal tissue has a major role in the control and regulation of physiological processes in the breast. Recently, the function of stroma in supporting the tumourigenic process as well as responding to the oncogenic lesion has become clearer. This review differs from the conventional view in that it focuses on and discusses the newly available evidence that points to the fact that mammary stroma has a significant contribution in actively generating transformed lesions and tumours. As such, the oncogenic signals can be dependent or independent of genetic mutations in mammary stromal cells. As a supportive and responsive agent in tumourigenesis, the stroma is induced by tumour cells to express critical signals that drive proliferation, angiogenesis, and motility while suppressing cell death. As an oncogenic agent in tumourigenesis, the stroma can provoke tumourigenicity in adjacent cells in the absence of pre-existing tumour cells leading to the acquisition of genomic changes. Investigating the mechanism by which the tumourigenic cues of the stroma facilitate the generation of malignant epithelial cells will provide invaluable insights into the oncogenic process.
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Stromal fibroblasts from 230 cancerous tumors of different localization were studied. Fibroblasts were located in the stroma of cancerous tumors relatively uniformly - on average 2430.9 133.7 per 1 mm2 stroma, but since the stroma occupied only a part of tumors, the number of fibroblasts per 1 mm2 histological preparation of neoplasm was somewhat lower and varied from 58.1 to 2772.0 (on average 1114.4 107.8), and in some cases fibroblasts were the prevailing cell type. The axial orientation of these stromal cells, especially in the areas of mature stroma, mostly coincided with the direction of collagen fiber bundles, and in the areas of edematous and disorganized connective tissue was often chaotic.
Cancer-Associated Fibroblasts
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