Induction of PA2.26, a cell-surface antigen expressed by active fibroblasts, in mouse epidermal keratinocytes during carcinogenesis

Gandarillas, Alberto; Scholl, Francisco G.; Benito, N; Gamallo, Carlos; Quintanilla, Miguel

doi:10.1002/(sici)1098-2744(199709)20:1<10::aid-mc3>3.0.co;2-m

Cited by 88 publications

(114 citation statements)

References 27 publications

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“…We also showed that the CT cells are non-smooth muscle and non-blood endothelial cells. Furthermore, podoplanin/PA2.26 has been reported to be upregulated in vivo on murine dermal fibroblast-like cells in activated wounded skin, on cultured fibroblasts (Gandarillas et al 1997) and on a mouse osteoblastic cell line (Nose et al 1990). In the ED specimens, we found podoplanin-expressing CT cells in bone cavities surrounding the VA and juxta-positioned to the margin of the bone matrix.…”

Section: Discussionmentioning

confidence: 99%

“…Podoplanin is a membrane bound glycoprotein shown to be important for the formation of cell surface protrusions and to promote migration and adhesion (Schacht et al 2003;Martin-Villar et al 2005). In dermis podoplanin seems to be induced on interstitial CT cells during inflammation and carcinogenesis (Gandarillas et al 1997). Interestingly, ectopic expression of PA2.26/podoplanin in mouse keratinocytes induces an epithelial-fibroblastoid morphological conversion or trans-differentiation to a phenotype with increased plasma membrane projections and enhanced motility (Scholl et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…or E11 antigen, originally found selectively expressed on alveolar type I-cells in the rat lung (Rishi et al 1995;Wetterwald et al 1996;Williams et al 1996). It is also homologous to the mouse glomerular membrane protein gp38P (Boucherot et al 2002), the OTS-8 gene product in cultured mouse osteoblasts (Nose et al 1990) and the 45 kD protein PA2.26, originally identified as a cell-surface antigen induced in keratinocytes during mouse skin carcinogenesis and in dermal fibroblast-like cells during wound healing (Gandarillas et al 1997). Although little is known about the biological functions of podoplanin, T1!podoplanin _ / _ mice die at birth due to respiratory failure and have defects in lymphatic vessel formation (Schacht et al 2003).…”

Section: Introductionmentioning

confidence: 99%

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An Interstitial Network of Podoplanin-Expressing Cells in the Human Endolymphatic Duct

Ekwall

Mayerl

Rubin

et al. 2006

JARO

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The human endolymphatic duct (ED) with encompassing interstitial connective tissue (CT) is believed to be important for endolymph resorption and fluid pressure regulation of the inner ear. The periductal CT cells are interconnected via numerous cellular extensions, but do not form vessel structures. Here we report that the periductal CT is populated by two distinct cell phenotypes; one expressing podoplanin, a protein otherwise found on lymph endothelia and on epithelia involved in fluid fluxes, and a second expressing a fibroblast marker. A majority of the interstitial cells expressed podoplanin but not the lymphatic endothelial cell markers hyaluronan receptor (LYVE-1) or vascular endothelial growth factor receptor-3 (VEGFR-3). The fibroblast marker positive cells were found close to the ED epithelium. In the mid-and distal parts of the ED, these cells were enriched under folded epithelia. Furthermore, subepithelial CT cells were found to express activated platelet derived growth factor (PDGF)-" receptors. Cultured CT cells from human inner ear periductal and perisaccular explant tissues were identified as fibroblasts. These cells compacted a three-dimensional collagen lattice by a process that could be promoted by PDGF-BB, a factor involved in interstitial fluid pressure regulation. Our results are compatible with the notion that the periductal CT cells are involved in the regulation of inner ear fluid pressure. By active compaction of the periductal CT and by the formation of villous structures, the CT cells could modulate fluid fluxes over the ED epithelium as well as the longitudinal flow of endolymph in the ED.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An Interstitial Network of Podoplanin-Expressing Cells in the Human Endolymphatic Duct

Ekwall

Mayerl

Rubin

et al. 2006

JARO

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“…In addition, podoplanin can induce platelet aggregation in vitro . In pathological situations studied thus far, the mouse homologue of podoplanin (PA2.26, OTS-8) is induced in mouse skin during tissue regeneration after wounding and treatment with carcinogenic phorbol 12-myristate 13-acetate (Gandarillas et al, 1997). OTS-8 is also induced by 12-Otetradecanoylphorbol-13-acetate in mouse osteoblastic cells and is constitutively expressed in oncogenic Ras-transformed cells (Nose et al, 1990).…”

Section: Podoplanin Is Expressed In Most Human Tissuesmentioning

confidence: 99%

The potential role of podoplanin in tumour invasion

2006

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“…In pathological situations studied thus far, the mouse homolog of podoplanin is induced in mouse skin during tissue regeneration after wounding. 6 The homolog is also constitutively expressed in oncogenic Ras-transformed cells. 7 These Key words: head and neck squamous cell carcinoma (HNSCC), oral cavity, oropharynx, podoplanin, immunohistochemistry, tissue microarray, sentinel node biopsy *S.J.S.…”

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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

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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...

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Induction of PA2.26, a cell-surface antigen expressed by active fibroblasts, in mouse epidermal keratinocytes during carcinogenesis

Cited by 88 publications

References 27 publications

An Interstitial Network of Podoplanin-Expressing Cells in the Human Endolymphatic Duct

An Interstitial Network of Podoplanin-Expressing Cells in the Human Endolymphatic Duct

The potential role of podoplanin in tumour invasion

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

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