Browsing by Subject "Podoplannin"

Now showing 1 - 4 of 4
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    Lymphangiogenesis and its role in cancer
    (Murcia : F. Hernández, 2005) Al-Rawi, M.A.A.; Mansel, R.E.; Jiang, W.G.
    In many tumour types, lymphatic vasculature serves as a major route for tumour metastasis. The dissemination of malignant cells to the regional lymph nodes is an early step in the progression of many solid tumours and is an important determinant of prognosis. Lymphangiogenesis (formation of new lymphatic vessels) is thought to be crucial for cancer cells to metastasise to the regional lymph nodes. However research in this important process has been neglected largely due to the lack of molecular markers specific to the lymphatic endothelium. Recently, several specific markers have been identified including LYVE-1, podoplanin and prox-1. Although the biology of lymphangiogeneis, particularly its regulation, is still far from clear, it is now well established that tumours are lymphangiogenic i.e. they could induce the generation of their own lymphatics and metastasise to the regional lymph nodes. It is thought that the interruption of the main signalling pathways involved in this process could help to prevent lymphatic spread of many tumours. Furthermore, understanding the molecular mechanisms in lymphangiogenesis might help to develop new therapeutic strategies against cancer lymphatic spread. Here, we reviewed the literature in regards to the biology of lymphangiogenesis, its molecular regulation, lymphatic markers and the significance in human solid tumours.
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    Podoplanin expression in tumor-free resection margins of oral squamous cell carcinomas: an immunohistochemical and fractal analysis study
    (Murcia: F. Hernández, 2010) Margaritescu, C.; Raica, M.; Pirici, D.; Simionescu, C.; Mogoanta, L.; Stinga, A.C.; Stinga, A.S.; Ribatti, Doménico
    Podoplanin is involved in tumorigenesis and cancer progression in head and neck malignancies and its expression is not restricted to lymphatic vessel endothelium. The aim of this study was to establish podoplanin expression in the tumor-free resection margins of oral squamous cell carcinomas (OSCCs) and to evaluate the geometric complexity of the lymphatic vessels in oral mucosa by utilizing fractal analysis. As concerns the podoplanin expression in noncancerous tissue, forty tumor-free resection margins from OSCCs were investigated utilizing immunohistochemistry for D2-40 antibody and image densitometry analysis. Podoplanin expression was extremely low in basal cells, especially in resection margins of OSCCs developed in the lower lip regions. However, a highly variable D2-40 expression in tumor-free resection margins associated with hyperplastic or dysplastic lesions was identified. Moreover, podoplanin expression also extended to the basal layer of the lower lip skin appendages, the myoepithelial cells of acini and ducts of minor salivary glands, and other structures from the oral cavity. As concerns the study of the density and complexity of oral lymphatic vessels architecture by means of immunohistochemistry (D2-40, CD31 and Ki-67 antibodies) and fractal analysis, we demonstrated that in normal oral mucosa the geometry of the lymphatic vessels was less complex at the level of the lower lip compared to the anterior part of the oral floor mucosa or the tongue. A comparative analysis between the normal and pathological aspects revealed statistically significant differences between the fractal dimension (FD) of the vessels’ outline, especially in the tongue. Fractal analysis proved an increasing lymphatic network complexity from normal to premalignant oral mucosal lesions, providing additional prognostic information in oral malignant tumors
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    Role of podoplanin expression in squamous cell carcinoma of upper aerodigestive tract
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Chuang, Wen-Yu; Chang, Yu-Sun; Yeh, Chi-Ju; Wu, Yi-Chin; Hsueh, Chuen
    Podoplanin, a type-1 transmembrane glycoprotein, was originally named due to its expression in renal podocytes of rats. It was subsequently detected in a variety of normal human tissues, including lymphatic endothelium. Although podoplanin has been identified as the endogenous ligand of C-type lectin-like receptor 2 (CLEC-2) on platelets, its physiological functions and pathways remain largely unknown. A role in lymphangiogenesis has been suggested, since podoplanin-deficient mice were found to die at birth with a phenotype of dilated, malfunctioning lymphatic vessels and lymphedema. Podoplanin is invariably expressed in some tumors, such as lymphangioma, seminoma and follicular dendritic cell tumor, but tumor cell expression of podoplanin is highly variable in squamous cell carcinoma (SCC). It has been found that high podoplanin expression is associated with lymph node metastasis and poor prognosis in SCC of the upper aerodigestive tract. Now there is growing evidence that podoplanin is also involved in carcinogenesis, cell motility, tumor invasiveness, platelet aggregation and hematogenous metastasis. Additionally, animal studies confirmed some in vivo effects of podoplaninoverexpressing tumors, including formation of more tumor lymphatic vessels, larger lymph node metastases, more platelet aggregation, and more pulmonary metastases. Several recently developed anti-podoplanin antibodies, such as NZ-1, P2-0 and hP2-0, have been shown to attenuate podoplanin-induced platelet aggregation and prevent experimental hematogenous metastasis in nude mice. These antibodies may be applied in preclinical and clinical studies to evaluate the possibility of podoplanin-targeted therapy.
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    Tumor cell expression of podoplanin correlates with nodal metastasis in esophageal squamous cell carcinoma
    (Murcia : F. Hernández, 2009) Chuang, Wen-Yu; Yeh, Chi-Ju; Wu, Yi-Chin; Chao, Yin-Kai; Liu, Yun-Hen; Tseng, Chen-Kan; Chang, Hsien-Kun; Liu, Hui-Ping; Hsueh, Chuen
    Podoplanin is a mucin-like glycoprotein expressed in the lymphatic endothelium. It has been suggested to play a role in lymphangiogenesis, since podoplanin deficient mice were found to have dilated malfunctioning lymphatic vessels and lymphedema. High podoplanin expression in tumor cells was found to correlate with lymph node metastasis and poor clinical outcome in patients with oral squamous cell carcinoma (SCC). However, the prognostic significance of podoplanin expression in esophageal SCC remains unexplored. Herein, we studied podoplanin expression in 59 patients who underwent surgical resection of esophageal SCC, with 43 of them preceded by preoperative concurrent chemoradiotherapy (CCRT). We found that high podoplanin expression strongly correlated with clinical nodal metastasis (cN1; p=0.0063), which was associated with short survival (p=0.012). However, there was no direct association between high podoplanin expression and short survival. We also found that lymphatic vessel invasion in the resected esophagus was strongly associated with pathological nodal metastasis (pN1; p=0.00092). Our results suggest that podoplanin could also play a role in tumor aggressiveness in esophageal SCC, as well as in oral SCC.