Enhanced Expression of Aggrus (T1alpha/Podoplanin), a Platelet-Aggregation-Inducing Factor in Lung Squamous Cell Carcinoma

Abstract

Aggrus (T1α/podoplanin, known as a specific marker for type I alveolar cells or lymphatic endothelial cells) is a transmembrane sialoglycoprotein that aggregates platelets. Previously, we showed that upregulated expression of Aggrus occurs in colorectal tumors or testicular tumors and could be associated with platelet-aggregating activity and metastatic ability. In testicular tumors, Aggrus is specifically expressed in seminoma. The present study investigates Aggrus expression in human primary lung cancer tissues of different types. Microarray analysis demonstrated that aggrus was significantly expressed in squamous cell carcinoma (10/15; 66.7%). Immunohistochemical analysis also showed that the incidence of positive staining in sections of squamous cell carcinoma (7/8; 87.5%) was higher than that in adenocarcinoma (2/13; 15.4%). Furthermore, Aggrus expression was detected in a squamous cell carcinoma cell line, NCI-H226, by real-time PCR. These findings indicated that overexpression of Aggrus occurred in squamous cell carcinoma of the lung. Therefore, Aggrus could be a useful diagnostic marker for squamous cell carcinoma of the lung.

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

“…23 In vitro studies suggested that podoplanin may be involved in mediating cell motility and adhesion. 23,24 Very recently, podoplanin expression was reported in squamous cell carcinomas of the epidermis, 13 oral cavity, 24 and lung, 25 and it was suggested that it may be involved in tumor cell invasion, metastasis, and tumor progression. In addition, mucin-type glycoproteins, such as podoplanin, are expressed widely on human normal cells and tumors [26][27][28] and have recently been implicated in cellular signaling, cell adhesion, tumor growth, and suppression of apoptosis.…”

The potential role of podoplanin in tumour invasion

“…The expression of podoplanin is upregulated in a number of different human cancers, including squamous cell carcinoma of the oral cavity, the larynx, the lung, the cervix, the oesophagus, and the skin, in dysgerminomas of the ovary and granulosa cell tumours, in mesothelioma, and in many tumours of the central nervous system (CNS) (Kato et al, 2005;Kimura and Kimura, 2005;Martin-Villar et al, 2005;Schacht et al, 2005;Shibahara et al, 2006;Wicki et al, 2006). The oncofetal M2A antigen expressed in testicular germ cell tumours is identical to podoplanin (Dumoff et al, 2005).…”

Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition

“…Podoplanin expression is upregulated in different types of experimental and human tumors, including squamous cell carcinomas of the skin, lung, esophagus, cervix, larynx and oral cavity (Gandarillas et al, 1997;Martín-Villar et al, 2005;Schacht et al, 2005;Kato et al, 2005;Wicki et al, 2006), colorectal adenocarcinomas , testicular germ cell tumors (Kato et al, 2004;Schacht et al, 2005) and mesotheliomas (Chu et al, 2005). In squamous cell carcinomas, podoplanin expression is frequently restricted to the invasive front (Martín-Villar et al, 2005;Wicki et al, 2006), and in some tumors correlates with downregulation of the cell-cell adhesion protein E-cadherin (Martín-Villar et al, 2005).…”