Characterization and cloning of the E11 antigen, a marker expressed by Rat Osteoblasts and Osteocytes

Wetterwald, Antoinette; Hofstetter, Willy; Cecchini, Marco; Lanske, Beate; Wagner, Charlotte; Fleisch, H.; Atkinson, Michael J.

doi:10.1016/8756-3282(95)00457-2

Cited by 268 publications

(216 citation statements)

References 25 publications

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“…[20][21][22] Antibodies to podoplanin, including D2-40, were reported to be selective markers for lymphatic endothelium and to be useful in identifying the presence of lymphatic invasion in various malignant neoplasms, including cervical carcinoma. [15][16][17] However, little is known about the biological function of podoplanin.…”

Section: Discussionmentioning

confidence: 99%

Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation

et al. 2006

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Lymphatic invasion and nodal metastasis are predictors of poor outcome in cervix carcinoma. We have recently found that low podoplanin immunoreactivity in cervix carcinoma correlated with the presence of lymphatic invasion and nodal metastasis. In the current study, we examined whether podoplanin expression in pretreatment cervical biopsies can predict the presence lymphatic invasion, nodal metastasis, and outcome in advanced-stage tumors treated by nonsurgical means. Podoplanin expression was analyzed by immunohistochemistry in 48 cervical biopsies and corresponding hysterectomy specimens of early-stage invasive squamous cell carcinoma and in 74 pretreatment biopsies from advanced-stage tumors treated with primary radiation. We found a highly significant correlation between podoplanin expression obtained in biopsy and corresponding hysterectomy materials (r ¼ 0.8962, Po0.0001). Low podoplanin expression showed a significant correlation with lymphatic invasion (Po0.0001) and nodal metastasis (P ¼ 0.0058). Low podoplanin expression in pretreatment biopsy material showed a significant correlation with poor disease-free (P ¼ 0.0009) and overall (P ¼ 0.0002) survival in advanced-stage tumors. Our results suggest that in advanced-stage cervix carcinomas treated by radiation, when traditional prognostic indicators are not available and treatment decisions are based on biopsy material and clinical staging parameters, examination of podoplanin expression in pretreatment biopsy material may be a useful marker to predict lymphatic metastasis and patient outcome. Prospective studies involving larger numbers of patients are needed to further evaluate the clinical utility of examination of podoplanin expression in patients with cervix carcinoma.

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Section: Discussionmentioning

confidence: 99%

Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation

et al. 2006

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“…OTS-8 was isolated as a phorbol ester-inducible gene from cultured osteoblasts (Nose et al, 1990), and gp38 was described as a marker of stromal cells in T-cell-dependent areas of peripheral lymphoid tissues (Farr et al, 1992). The rat (T1␣/E11/podoplanin), canine (gp40), and human (gp36) homologs to murine PA2.26 have also been reported by different laboratories (Breiteneder-Geleff et al, 1997;Rishi et al, 1995;Wetterwald et al, 1996;Zimmer et al, 1997Zimmer et al, , 1999. All these proteins have similar biochemical characteristics and tissular distributions.…”

Section: Discussionmentioning

confidence: 99%

Ectopic Expression of PA2.26 Antigen in Epidermal Keratinocytes Leads to Destabilization of Adherens Junctions and Malignant Progression

Scholl

Gamallo

Quintanilla

2000

Laboratory Investigation

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SUMMARY: PA2.26 antigen is a small mucin-type transmembrane glycoprotein induced in mouse epidermal keratinocytes during carcinogenesis. It is located at plasma membrane projections, such as microvilli and ruffles, where it interacts with the actin cytoskeleton. Previous studies revealed that ectopic expression of PA2.26 in epidermal MCA3D keratinocytes induces cell surface extensions and increased motility. Here, we show that PA2.26-expressing MCA3D (3D2.26) cell transfectants undergo a phenotypic conversion linked to the acquisition of malignant characteristics. The 3D2.26 cells down-regulate basal keratin K14 and up-regulate vimentin and keratin K8 expression. Immunofluorescence analysis in 3D2.26 cell cultures showed loss of cortical actin filaments and destabilization of adherens junctions mediated by E-and P-cadherin, although both cadherin mRNAs were expressed in the transfectants. When the cadherin protein levels were analyzed in Western blots, no P-cadherin protein or smaller polypeptide E-cadherin forms were detected, suggesting that E-and P-cadherin synthesized in 3D2.26 cells was unstable and proteolytically degraded. Transplantation of 3D2.26 cells into athymic nude mice induced tumors, whereas MCA3D cells and control (3DN) transfectants were not tumorigenic after 72 days postinjection. The phenotype of the tumors was undifferentiated, with mixed regions exhibiting a glandular differentiation pattern in which the presence of numerous surface microvilli was observed at the ultrastructural level. Interestingly, PA2.26 antigen was highly expressed in these microvillous cell surfaces. Tumor cells were vimentin-and K8-positive and showed an aberrant pattern of E-cadherin protein expression in which large cytoplasmic aggregates were found close to the nucleus. Infiltration of tumor cells into lymphatic vessels and the presence of frequent regional lymph node metastases were also observed in the tumors. These results indicate that expression of PA2.26 antigen in premalignant keratinocytes induces a fully transformed and metastatic phenotype, and they suggest an involvement of PA2.26 in malignant progression. (Lab Invest 2000, 80:1749 -1759. P A2.26 antigen was identified as a cell-surface protein of about 45 kDa induced in basal-like keratinocytes and dermal fibroblasts during mouse epidermal carcinogenesis and skin remodeling processes. PA2.26 is absent from cultured nontumorigenic keratinocytes, but it is expressed in carcinoma cell lines and cultured active fibroblasts (Gandarillas et al, 1997). The molecular and biochemical characterization of PA2.26 revealed that it is a small mucin-like transmembrane sialoglycoprotein of 172 amino acids, located at microvilli, filopodia, lamellipodia, and ruffles. In normal tissues, PA2.26 is expressed in different type of cells: in the epithelia of choroid plexuses, ependyma, glomeruli, and alveoli, in all mesothelia, and in endothelia of lymphatic vessels, always concentrated at the apical plasma membranes and microvillous projections (Scholl et al, 1999).OTS-8 an...

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“…Podoplanin is homologous to the T1! 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).…”

Section: Introductionmentioning

confidence: 99%

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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Characterization and cloning of the E11 antigen, a marker expressed by Rat Osteoblasts and Osteocytes

Cited by 268 publications

References 25 publications

Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation

Low podoplanin expression in pretreatment biopsy material predicts poor prognosis in advanced-stage squamous cell carcinoma of the uterine cervix treated by primary radiation

Ectopic Expression of PA2.26 Antigen in Epidermal Keratinocytes Leads to Destabilization of Adherens Junctions and Malignant Progression

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

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