The potential role of podoplanin in tumour invasion

Wicki, Andreas; Christofori, Gerhard

doi:10.1038/sj.bjc.6603518

Cited by 276 publications

(347 citation statements)

References 29 publications

Supporting

Mentioning

310

Contrasting

Unclassified

Order By: Relevance

“…152,157 PDPN is predominantly found at the invasive front of many tumors, which is consistent with its role in promoting malignant invasion. 152,158 For example, PDPN expression is strongly induced in about 40% of breast cancers, 158,159 over 50% of oral cancers, 160,161 and about 80% of skin cancers. 162,163 Antibodies against PDPN and a PDPN interacting partner (tetraspanin CD9) can inhibit lung metastasis of CHO cells transfected with PDPN.…”

Section: Src and Downstream Chemotherapeutic Targetssupporting

confidence: 53%

“…Pdpn associates with ezrin and regulates the activities of Rho GTPases to promote filopodia formation, cell motility, and metastasis. [152][153][154] Pdpn expression is induced by tumor promoters, including TPA, RAS, and Src, 127,155,156 and enhances transformed cell motility and invasion. 152,157 PDPN is predominantly found at the invasive front of many tumors, which is consistent with its role in promoting malignant invasion.…”

Section: Src and Downstream Chemotherapeutic Targetsmentioning

confidence: 99%

“…[152][153][154] Pdpn expression is induced by tumor promoters, including TPA, RAS, and Src, 127,155,156 and enhances transformed cell motility and invasion. 152,157 PDPN is predominantly found at the invasive front of many tumors, which is consistent with its role in promoting malignant invasion. 152,158 For example, PDPN expression is strongly induced in about 40% of breast cancers, 158,159 over 50% of oral cancers, 160,161 and about 80% of skin cancers.…”

Section: Src and Downstream Chemotherapeutic Targetsmentioning

confidence: 99%

See 2 more Smart Citations

Src Points the Way to Biomarkers and Chemotherapeutic Targets

Krishnan¹,

Miller

Goldberg³

2012

Genes & Cancer

View full text Add to dashboard Cite

The role of Src in tumorigenesis has been extensively studied since the work of Peyton Rous over a hundred years ago. Src is a non-receptor tyrosine kinase that plays key roles in signaling pathways controlling tumor cell growth and migration. Src regulates the activities of numerous molecules to induce cell transformation. However, transformed cells do not always migrate and realize their tumorigenic potential. They can be normalized by surrounding nontransformed cells by a process called contact normalization. Tumor cells need to override contact normalization to become malignant or metastatic. In this review, we discuss the role of Src in cell migration and contact normalization, with emphasis on Cas and Abl pathways. This paradigm illuminates several chemotherapeutic targets and may lead to the identification of new biomarkers and the development of effective anticancer treatments.

show abstract

Section: Src and Downstream Chemotherapeutic Targetssupporting

confidence: 53%

Section: Src and Downstream Chemotherapeutic Targetsmentioning

confidence: 99%

Section: Src and Downstream Chemotherapeutic Targetsmentioning

confidence: 99%

See 1 more Smart Citation

Src Points the Way to Biomarkers and Chemotherapeutic Targets

Krishnan¹,

Miller

Goldberg³

2012

Genes & Cancer

View full text Add to dashboard Cite

show abstract

“…26,27 Recent experimental results have demonstrated that podoplanin mediates a pathway leading to collective cell migration and invasion in vitro. 14,28 The forced expression of podoplanin led to a dramatic change of cellular morphology with a significant decrease of cellular stress fibers and a concomitant formation of filopodia-like membrane protrusions. Accordingly, adhesion and spreading of cells on the extracellular matrix protein fibronectin were enhanced by podoplanin expression.…”

Section: Discussionmentioning

confidence: 99%

Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx

Huber

Fritzsche

Züllig

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

In patients with early head and neck squamous cell carcinoma (HNSCC), occult lymph node metastasis is difficult to predict by clinical or pathological parameters. However, such parameters are necessary to select patients either for elective neck dissection or the sentinel lymph node (SLN) procedure. The membrane glycoprotein podoplanin is normally expressed in lymphatic endothelial cells. Recently, expression of podoplanin by cancer cells was demonstrated to promote tumor cell motility and tumor lymphangiogenesis in vitro. The value of cancer cell-expressed podoplanin was to be determined as a predictive marker for SLN metastasis in early HNSCC of the oral cavity and oropharynx. One hundred twenty patients with HNSCC of the oral cavity and oropharynx undergoing a SLN biopsy were enrolled in this prospective clinical trial of SLN biopsy. Cancer cell-expressed podoplanin was determined by immunohistochemistry using tissue microarrays. Podoplanin expression was quantified by the intensity reactivity score and categorized into expression and nonexpression. SLN examination revealed occult metastasis in 45 patients (37.5%). Twenty-nine of 120 (24.2%) primary HNSCC showed podoplanin expression. Podoplanin expression correlated significantly with SLN metastasis (p 5 0.029) and remained a significant predictor for lymph node status even after controlling for tumor stage (p 5 0.028). As a predictive marker for SLN metastasis, however, podoplanin expression reached a sensitivity of a mere 36% and a specificity of 83%. Podoplanin expression is associated with metastasis to lymph nodes in vivo. Podoplanin immunohistochemistry in early HNSCC of the oral cavity and oropharynx may help to select patients for the SLN procedure and to identify patients with increased risk for presence of occult lymph node metastasis in the neck.Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide and responsible for more than 7,800 deaths per year in the United States alone. 1 Despite improvements in surgical treatment and radiation technology over the last decades, survival has not significantly improved. A chief feature of malignant behavior is the capability of tumor cells to metastasize to other organs. Metastasis of many human cancers, including HNSCC, occurs primarily through the lymphatic system. The cellular mechanisms responsible for the acquisition of a metastatic phenotype include the adaptation to potential hostile environment (blood stream, lymph nodes and organ of metastasis). In addition, the ''tumor cell-to-tumor cell'' and ''tumor cell-to-stromal environment'' cross talk is recognized as an important condition for invasion and metastasis.Very recently, expression of the 38-kDa Type 1 transmembrane glycoprotein podoplanin has been shown to induce tumor lymphangiogenesis and enhance metastasis to lymph nodes. 2,3 Human podoplanin is expressed in various normal human tissues. Podoplanin is highly and specifically expressed in lymphatic endothelial cells, but not in blood vessel endothelium. 4,5...

show abstract

“…In addition, podoplanin was also expressed in several tumors, including squamous cell carcinoma, germ cell tumor, and mesothelioma, raising a possibility that it may have biologic functions in tumor cells. [35][36][37] Thus, immunohistochemical examination of D2-40-positive non-lymphatic cells was explored to understand tumor progression.…”

mentioning

confidence: 99%

Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

et al. 2008

View full text Add to dashboard Cite

Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P ¼ 0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P ¼ 0.0315 and P ¼ 0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63%, 24/38) and in the tumor periphery (79%, 30/38) than in the tumor center (27%, 9/ 38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P ¼ 0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80%) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P ¼ 0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P ¼ 0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.

show abstract

The potential role of podoplanin in tumour invasion

Cited by 276 publications

References 29 publications

Src Points the Way to Biomarkers and Chemotherapeutic Targets

Src Points the Way to Biomarkers and Chemotherapeutic Targets

Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx

Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

Contact Info

Product

Resources

About