Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma

Miyahara, Mayumi; Tanuma, Jun‐ichi; Sugihara, Kazumasa; Semba, Ichiro

doi:10.1002/cncr.22900

Cited by 114 publications

(139 citation statements)

References 32 publications

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“…Our findings contrast with the observations for HNSCCs, particularly for SCC affecting the oral cavity, which is also a common site for salivary carcinomas [7,8,15]. In HNSCC, LVD measurements have been suggested as potential indicators of the risk of lymph node metastasis [6][7][8][9].…”

Section: Discussioncontrasting

confidence: 99%

Lymphatic vessel density and expressions of lymphangiogenic growth factors in salivary carcinomas

Mf¹,

Af²,

Ll³

et al. 2011

neo

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Nodal metastasis is an important prognostic indicator in head and neck cancers, including salivary carcinomas. In these, the risk for lymph node metastasis is variable and strongly associated with the tumor histologic type. The aim of the current study was to evaluate the lymphatic vessel density (LVD) and expressions of lymphangiogenic growth factors by tumor cells in different histologic types of salivary carcinomas subdivided according to the risk for nodal metastasis. In 15 high-risk (undifferentiated, high-grade mucoepidermoid and salivary duct carcinomas) and 60 low/moderate-risk tumors (adenoid cystic, low/intermediate-grade mucoepidermoid, acinic cell, myoepithelial, epithelial-myoepithelial and polymorphic lowgrade carcinomas) the expressions of vascular endothelial growth factor-C (VEGF-C), hepatocyte growth factor (HGF) and D2-40 (for assessing LVD) were examined. No significant differences were encountered between high-and low/moderate/-risk carcinomas regarding LVD and VEGF-C or HGF expressions. Furthermore, the expression of these proteins did not correlate with LVD. Lymphatic vascular invasion was found mainly in high-risk carcinomas. Intratumoral LVD was significantly lower than peritumoral, regardless of the risk for metastasis and primary site of the lesion. The histologic types of salivary carcinomas which are associated with high-risk for nodal metastasis do not present increased LVD or VEGF-C and HGF expressions. The greater tendency for metastasis in these carcinomas seems to be related to their capacity to invade lymph vessels. Further studies on tumor cell interactions with lymphatic endothelial cells are needed to improve our understanding of the metastatic potential of salivary carcinomas. Key words: lymph vessels, salivary carcinoma, VEGF-C, HGF.Nodal metastasis is an important prognostic predictor in head and neck cancers, including salivary carcinomas. The risk for lymph node metastasis in these carcinomas is highly variable (9% -85%) [1] and strongly associated with the tumor histologic type [1][2][3][4][5]. It is a general consensus that high-grade mucoepidermoid carcinomas, salivary duct carcinomas, undifferentiated carcinomas and squamous cell carcinomas are high-risk tumors for nodal metastasis [1,[3][4][5]. In these the risk for neck metastasis has been described to be >50% [1] and, thus, elective neck dissection is considered in their management [1][2][3].Lymph vessels provide the main avenue for nodal metastasis and in head and neck squamous cell carcinoma (HNSCC) it has been shown that tumors of different anatomic regions do not vary significantly in their lymphangiogenic properties [6,7]. However, a high lymph vessel density (LVD) seems to be an indicator of the risk of lymph node metastasis in HNSCC [6][7][8][9]. Regarding salivary gland tumors, the lymphatic vessels have rarely been studied [10][11][12] and in a particular type of salivary carcinoma, i.e. in those arising in pleomorphic adenomas (CXPA) the lymphatic network was found to be composed mainly of pre-existing ...

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Section: Discussioncontrasting

confidence: 99%

Lymphatic vessel density and expressions of lymphangiogenic growth factors in salivary carcinomas

Mf¹,

Af²,

Ll³

et al. 2011

neo

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“…Although tumor cell dissemination is mediated by a number of mechanisms, the most common pathway of initial dissemination is through the lymphatic system to the regional lymph nodes (Pepper et al, 2000). The presence of metastases in regional lymph nodes is a strong indicator of low-patient survival rate, poor patient prognosis in many types of cancer (Skobe et al, 2001;Miyahara et al, 2007;Liu et al, 2008). Despite advances in the treatment of breast cancer, morbidity and mortality from breast cancer remain unacceptably high.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental tumor models and human clinicopathologic data indicate that lymphangiogenesis and lymph node metastasis are important prognostic indicators for the spread of cancer (Eccles et al, 2007;Miyahara et al, 2007). Moreover, lymphangiogenesis induced by breast cancer correlates with lymph node metastasis and promotes metastasis (Skobe et al, 2001).…”

mentioning

confidence: 99%

Lentivirus‐Mediated Small Interfering RNA Targeting VEGF‐C Inhibited Tumor Lymphangiogenesis and Growth in Breast Carcinoma

Guo

Zhang

Luo

et al. 2009

The Anatomical Record

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“…It is well known that lymphangiogenesis in peritumoral area and lymph node contributes to tumor metastasis through tumor-draining lymph nodes (31,32). EPO is a growth factor with pleiotropic effects.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

et al. 2011

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Cancer therapy often produces anemia, which is treated with erthropoietin (EPO) to stimulate erythrocyte production. However, concerns have recently arisen that EPO treatment may promote later tumor metastasis and mortality. The mechanisms underlying such effects are unknown, but it is clear that EPO has pleiotropic effects in cell types other than hematopoietic cells. In this study, we investigated how EPO affects lymphangiogenesis and lymph node tumor metastasis in mouse models of breast cancer and melanoma. In these models, EPO increased lymph node lymphangiogenesis and lymph node tumor metastasis in a manner associated with increased migration, capillary-like tube formation, and doseand time-dependent proliferation of human lymphatic endothelial cells. EPO increased sprouting of these cells in a thoracic duct lymphatic ring assay. These effects were abrogated by cotreatment with specific inhibitors of phosphoinositide 3-kinase or mitogen-activated protein kinase, under conditions in which EPO increased Akt and extracellular signal-regulated kinase 1/2 phosphorylation. Intraperitoneal administration of EPO stimulated peritoneal lymphangiogenesis, and systemic treatment of EPO increased infiltration of CD11b þ macrophages in tumor-draining lymph nodes. Finally, EPO increased VEGF-C expression in lymph node-derived CD11b þ macrophages as well as in bone marrow-derived macrophages in a dose-and time-dependent manner. Our results establish that EPO exerts a powerful lymphangiogenic function and can drive both lymph node lymphangiogenesis and nodal metastasis in tumor-bearing animals. Cancer Res; 71(13); 4506-17. Ó2011 AACR.

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Tumor lymphangiogenesis correlates with lymph node metastasis and clinicopathologic parameters in oral squamous cell carcinoma

Cited by 114 publications

References 32 publications

Lymphatic vessel density and expressions of lymphangiogenic growth factors in salivary carcinomas

Lymphatic vessel density and expressions of lymphangiogenic growth factors in salivary carcinomas

Lentivirus‐Mediated Small Interfering RNA Targeting VEGF‐C Inhibited Tumor Lymphangiogenesis and Growth in Breast Carcinoma

Erythropoietin Induces Lymph Node Lymphangiogenesis and Lymph Node Tumor Metastasis

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