High-level expression of podoplanin in benign and malignant soft tissue tumors: Immunohistochemical and quantitative real-time RT-PCR analysis

Xu, Yongjun; Ogose, Akira; Kawashima, Hiroyuki; Hotta, Tomomitsu; Ariizumi, Takashi; Li, Guidong; Umezu, Hajime; Endo, Naoto

doi:10.3892/or.2011.1141

Cited by 13 publications

(8 citation statements)

References 41 publications

(45 reference statements)

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“…In humans, podoplanin staining in the absence of cytokeratin staining can be seen in several different sarcomas as well as in malignant mesothelioma [34,97]. The malignant serosal tumors seen in this study were morphologically consistent with malignant sarcomatous mesotheliomas with five of the six tumors involving multiple peritoneal serosal surfaces.…”

Section: Discussionsupporting

confidence: 51%

Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes

et al. 2014

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BackgroundEngineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNT (5 mg/m3, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation.ResultsTwenty-three percent of the filtered air controls, 26.5% of the MWCNT-exposed, and 51.9% of the MCA-exposed mice, had lung bronchiolo-alveolar adenomas and lung adenocarcinomas. The average number of tumors per mouse was 0.25, 0.81 and 0.38 respectively. By contrast, 90.5% of the mice which received MCA followed by MWCNT had bronchiolo-alveolar adenomas and adenocarcinomas with an average of 2.9 tumors per mouse 17months after exposure. Indeed, 62% of the mice exposed to MCA followed by MWCNT had bronchiolo-alveolar adenocarcinomas compared to 13% of the mice that received filtered air, 22% of the MCA-exposed, or 14% of the MWCNT-exposed. Mice with early morbidity resulting in euthanasia had the highest rate of metastatic disease. Three mice exposed to both MCA and MWCNT that were euthanized early had lung adenocarcinoma with evidence of metastasis (5.5%). Five mice (9%) exposed to MCA and MWCNT and 1 (1.6%) exposed to MCA developed serosal tumors morphologically consistent with sarcomatous mesotheliomas, whereas mice administered MWCNT or air alone did not develop similar neoplasms.ConclusionsThese data demonstrate that some MWCNT exposures promote the growth and neoplastic progression of initiated lung cells in B6C3F1 mice. In this study, the mouse MWCNT lung burden of 31.2 μg/mouse approximates feasible human occupational exposures. Therefore, the results of this study indicate that caution should be used to limit human exposures to MWCNT.

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Section: Discussionsupporting

confidence: 51%

Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes

et al. 2014

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“…The present study also showed both the cytoplasmic and membrane positivity being higher in all the grades of SCC when compared to the only membrane positivity and this high expression could be attributed to the expression of podoplanin at the protein and mRNA levels. [ 18 ] Overall podoplanin expression was high in MDSCC when compared to PDSCC and WDSCC thereby reflecting the immature status in the differentiation process of SCC.…”

Section: Discussionmentioning

confidence: 99%

Expression of podoplanin in different grades of oral squamous cell carcinoma

Prasad¹,

Kashyap²,

Babu³

et al. 2015

Ann Med Health Sci Res

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Background:The expression of podoplanin is up-regulated in a number of different human cancers, including squamous cell carcinoma of the oral cavity and its relationship with tumor invasion raises the possibility that podoplanin expression could be used as a biomarker for diagnosis and prognosis.Aim:The aim of the present study is to evaluate the expression of podoplanin in different grades of squamous cell carcinoma (SCC) and to correlate the expression of podoplanin with relevant clinical features such as age, sex, site and associated habits.Materials and Methods:Retrospective study was carried on formalin fixed, paraffin embedded blocks of oral SCC (OSCC) from the archives of Department of Oral and Maxillofacial Pathology, Vishnu Dental College, Bhimavaram. Thirty diagnosed cases were included, of which 10 were well-differentiated SCC (WDSCC) (n = 10), 10 moderately DSCC and 10 poorly DSCC. Demographics including age, sex, gender and associated habit history, were recorded. Immunohistochemical staining was done with podoplanin anti D2–40 antibody, for all the cases of OSCC and assessed qualitatively. The data obtained were tabulated and subjected to statistical analysis.Results:In the present study, 27 cases of SCC showed podoplanin expression and remaining three cases showed no expression. The scoring criterion suggested by Yuan et al. was followed for semi-quantitative assessment. OSCC, seven cases presented weak expression (Immunoreactive score [IRS] 0–3), 15 presented moderate expression (IRS Score 4–7) and 5 presented high expression (IRS Score > 8). The assessment of podoplanin expression in the cytoplasm, the membrane and the cytoplasm and membrane (both) of tumor cells showed overall high positivity in the cytoplasmic followed by both and the membrane.Conclusion:Podoplanin could be a potent biomarker in assessing the cytoplasm/membrane staining of tumor cells. Furthermore, a high level of podoplanin expression is suggestive of high frequency of lymph node metastasis and immature status in the differentiation process of OSCC.

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“…PDPN is also expressed by normal kidney podocytes [15], alveolar type I cells [16], basal epidermal keratinocytes [17], and mesothelial cells [18,19]. Several types of cancer may also express PDPN, such as squamous cell carcinomas [20,21], soft tissue tumors [22], and brain tumors [23]. PDPN-expressing cancer cells have enhanced malignant potential due to enhancement of platelet aggregation, which promotes metastasis [24,25], alteration of cell morphology and motility [26,27], and epithelial-mesenchymal transition [28].…”

Section: Introductionmentioning

confidence: 99%

Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas

et al. 2013

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BackgroundInteractions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer.MethodsExpression of PDPN in pancreatic IDCs was assessed by immunohistochemical examination in 105 patients who underwent pancreatic resection. Primary CAFs were established from pancreatic cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis were performed to investigate PDPN expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the functional differences between PDPN+ CAFs and PDPN– CAFs using indirect co-culture with pancreatic cancer cell lines. We also investigated the culture conditions to regulate PDPN expression in CAFs.ResultsPDPN expression in stromal fibroblasts was associated with lymphatic vessel invasion (P = 0.0461), vascular invasion (P = 0.0101), tumor size ≥3 cm (P = 0.0038), histological grade (P = 0.0344), Union for International Cancer Control classification T stage (P = 0.029), and shorter survival time (P < 0.0001). Primary CAFs showed heterogeneous PDPN expression in vitro. Moreover, migration and invasion of pancreatic cancer cell lines (PANC-1 and SUIT-2) were associated with PDPN expression in CAFs (P < 0.01) and expression of CD10, matrix metalloproteinase (MMP) 2, and MMP3. In cultured CAFs, PDPN positivity changed over time under several conditions including co-culture with cancer cells, different culture media, and addition of growth factor.ConclusionsPDPN-expressing CAFs enhance the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an independent predictor of poor outcome. Understanding the regulation of the tumor microenvironment is an important step towards developing new therapeutic strategies.

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High-level expression of podoplanin in benign and malignant soft tissue tumors: Immunohistochemical and quantitative real-time RT-PCR analysis

Abstract: Abstract. Podoplanin is a 38 kDa mucin-type transmembrane glycoprotein that was first identified in rat glomerular epithelial cells (podocytes). It is expressed in normal lymphatic endothelium, but is absent from vascular endothelial cells.

Cited by 13 publications

References 41 publications

Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes

Promotion of lung adenocarcinoma following inhalation exposure to multi-walled carbon nanotubes

Expression of podoplanin in different grades of oral squamous cell carcinoma

Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas

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