Lymphatic Vessel Activation in Cancer

Cassella, Melanie; Skobe, Mihaela

doi:10.1111/j.1749-6632.2002.tb04873.x

Cited by 42 publications

(28 citation statements)

References 43 publications

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“…Moreover, in a retrospective prognostic study, Dadras et al (2003) found that the size of peritumourous lymphatic vessels was the most significant independent factor that correlates with LN metastasis in human malignant melanomas. However, other studies show that intratumourous and not peritumourous lymphatic vessels are vital for lymphatic metastasis (Beasley et The infiltration of lymphatic vessels into the tumour may have a passive role in cancer metastasis by creating an increased opportunity for metastatic tumour cells to leave the primary tumour site but might also establish a paracrine signalling pathway for tumour cell growth and invasion through the release of specific growth factors or chemokines (Cassella and Skobe, 2002). Michaela Skobe et al have shown that lymphatic capillaries activated by factors produced by tumours, such as VEGF-C, promote tumour cell invasion by increasing tumour cell transendothelial migration through the expression of the CC-type chemokine ligand 1 on LECs and its receptor CC-type chemokine receptor 8 on tumour cells .…”

Section: Methodology Of Lymphangiogenesis Quantification In Solid Tummentioning

confidence: 99%

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

et al. 2006

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The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra-and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment. Metastasis is the leading cause of cancer mortality. Metastatic cancer cells can escape from their site of origin and spread to distant organs through invasion of the vascular system and/or the lymphatic system. Tumour vascularisation is widely accepted as a bona fide indicator of tumour growth, metastases and patient survival. In 1996, Peter Vermeulen et al (1996) published a first international consensus on the methodology and criteria of the evaluation of angiogenesis quantification in solid tumours and 5 years later, a second consensus report, in which new concepts and mechanisms of tumour vascularisation were integrated, appeared (Vermeulen et al, 2002). Both reports were aimed at improving the standardisation of angiogenesis quantification in order to allow intratumourous microvessel density to be applied as a prognostic indicator and, moreover, as a reliable predictor of the risk of malignant transformation of premalignant lesions and of response to cancer treatment. Contrary to angiogenesis, the de novo formation of lymphatic vessels or lymphangiogenesis and its role in promoting the metastatic spread of tumour cells has only recently become a focal point of cancer research with an increasing number of studies showing a relationship between patient survival and lymphatic density in different tumour types. In order to confirm the potential prognostic value of lymphangiogenesis in patients with cancer, a quantification method that is characterised by a low intra-and interobserver variability needs to be developed. In this first consensus report, we would like to provide an overview of current concepts of the lymphatic vasculature and its regulating factors and propose guidelines for the estimation of the ongoing lymphangiogenesis in solid human tumour sections.

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Section: Methodology Of Lymphangiogenesis Quantification In Solid Tummentioning

confidence: 99%

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

et al. 2006

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“…Here, we aim to explore the association of CCR7 expression with lymph node metastasis in gastric carcinoma. Furthermore, activation of lymphatics by VEGF-C may promote production of chemoattractants such as CCL21 by lymphatic endothelial cells and thereby facilitate tumor cell positive for CCR7 expression entry into lymphatics [21] , so the other aim of this study is to investigate the value of the combined examination of VEGF-C and CCR7 expression in predicting lymph node metastasis of gastric carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Expression of vascular endothelial growth factor C and chemokine receptor CCR7 in gastric carcinoma and their values in predicting lymph node metastasis

Yan

Zhu²,

Yu³

et al. 2004

WJG

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AIM:To study the expression of vascular endothelial growth factor C (VEGF-C) and chemokine receptor CCR7 in gastric carcinoma and to investigate their associations with lymph node metastasis of gastric carcinoma and their values in predicting lymph node metastasis. METHODS:The expression of VEGF-C and CCR7 in gastric carcinoma tissues obtained from 118 patients who underwent curative gastrectomy was examined by immunohistochemistry. Among these patients, 39 patients underwent multi-slice spiral CT (MSCT) examination. RESULTS:VEGF-C and CCR7 were positively expressed in 52.5 and 53.4% of patients. VEGF-C expression was more frequently found in tumors with lymph node metastasis than those without it (P<0.001). VEGF-C expression was also closely related to lymphatic invasion (P<0.001), vascular invasion (P<0.01), and TNM stage (P<0.001). However, there was no significant correlation between VEGF-C expression and age at surgery, gender, tumor size, tumor location, Lauren classification, and depth of invasion. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P<0.001) and was also associated with tumor size (P<0.01), depth of invasion (P<0.001), lymphatic invasion (P<0.001), and TNM stage (P<0.001). However, the presence of CCR7 had no correlation to age at surgery, gender, tumor location, Lauren classification, and vascular invasion. Among the 39 patients who underwent MSCT examination, only CCR7 expression was related to lymph node metastasis determined by MSCT (P<0.05). In the current retrospective study, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of VEGF-C and CCR7 expression in the diagnosis of lymph node metastasis for patients with gastric carcinoma were 73.8%, 70.2%, 72.6%, 71.4% and 72.0%, and 82.0%, 77.2%, 79.4%, 80.0% and 79.7%, respectively. After subdivision according to the combination of VEGF-C and CCR7 expression, receiver operating characteristic (ROC) analysis showed that the accuracy of the combined examination of VEGF-C and CCR7 expression in predicting lymph node metastasis was relatively high (area under ROC curve [Az]=0.83). CONCLUSION:The expression of VEGF-C and CCR7 is related to lymph node metastasis of gastric carcinoma and both of them may become new targets for the treatment of gastric carcinoma. Furthermore, the combined examination of VEGF-C and CCR7 expression in endoscopic biopsy specimens may be useful in predicting lymph node metastasis of gastric carcinoma and deciding the extent of surgical lymph node resection.

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“…In recent years, the lack of lymphatic function in solid tumors has been identified as one cause for hindered delivery of chemotherapeutic drugs to solid tumors (Jain, 2001). Tumor metastasis is also thought to involve lymphatics as one, if not the primary, pathway (Cassella and Skobe, 2002;Skobe et al, 2001;Stacker et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Network Development in Biological Gels: Role in Lymphatic Vessel Development

Roose

Fowler

2008

Bull. Math. Biol.

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In this paper, we present a model that explains the prepatterning of lymphatic vessel morphology in collagen gels. This model is derived using the theory of two phase rubber material due to Flory and coworkers and it consists of two coupled fourth order partial differential equations describing the evolution of the collagen volume fraction, and the evolution of the proton concentration in a collagen implant; as described in experiments of Boardman and Swartz (Circ. Res. 92, 801-808, 2003). Using linear stability analysis, we find that above a critical level of proton concentration, spatial patterns form due to small perturbations in the initially uniform steady state. Using a long wavelength reduction, we can reduce the two coupled partial differential equations to one fourth order equation that is very similar to the Cahn-Hilliard equation; however, it has more complex nonlinearities and degeneracies. We present the results of numerical simulations and discuss the biological implications of our model.

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Lymphatic Vessel Activation in Cancer

Cited by 42 publications

References 43 publications

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours

Expression of vascular endothelial growth factor C and chemokine receptor CCR7 in gastric carcinoma and their values in predicting lymph node metastasis

Network Development in Biological Gels: Role in Lymphatic Vessel Development

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