Podoplanin in cancer cells is experimentally able to attenuate prolymphangiogenic and lymphogenous metastatic potentials of lung squamoid cancer cells

Molecular Cancer

Research

Seiji Nakamura¹  Yoshihiko Maehara²  Mitsuho Onimaru³  Katsuo Sueishi³  Hanako Suzuki⁴  Yoshikazu Yonemitsu⁵ 

[1] Department of Oral and Maxillofacial Surgery, Graduate School of Dental Sciences, Kyushu University, Fukuoka, Japan;Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;Department of Oral and Maxillofacial Surgery, Graduate School of Dental Sciences, Kyushu University, Fukuoka, Japan;R&D Laboratory for Innovative Biotherapeutics Graduate School of Pharmaceutical Sciences, Kyushu, University;

关键词: Lymphatic Vessel;    Lymphatic Endothelial Cell;    Lymphatic Vessel Density;    Squamous Cell Carcinoma Cell Line;    Lung Squamous Cell Carcinoma;   

DOI  :  10.1186/1476-4598-9-287

 received in 2010-01-18, accepted in 2010-10-31,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPodoplanin, a mucin-like transmembrane glycoprotein, is reportedly expressed in a variety of malignant cells and is generally regarded as a factor for promoting tumor progression in conventional studies. By contrast, a clinicopathologically conflicting role for podoplanin, namely as a favorable prognostic factor for patients with lung/cervical squamous cell carcinoma (SCC), has recently been reported. Here, we investigated the role of podoplanin expressed in lung squamoid cancer cells (LSCCs) in experimental tumor progression.ResultsUsing EBC-1 cells, a lung SCC cell line without podoplanin expression and with lymphogenous metastatic potential, stable transformants with or without an exogenous human podoplanin gene were established and applied to a mouse tumor implantation model. In vivo examinations revealed that exogenous podoplanin had no influence on tumor growth, whereas it significantly restrained axillary lymph node metastasis associated with the suppression of lymphangiogenesis but not angiogenesis and with the downregulation of EBC-1-derived VEGF-C but not other lymphangiogenesis-related factor mRNAs in implanted tumor tissue. In vitro examinations to clarify the mechanisms underlying the in vivo phenomena revealed that exogenous podoplanin significantly suppressed the expression of VEGF-C mRNA and of the protein, and also increased the level of phosphorylated c-jun N terminal kinase (JNK) in EBC-1 cells. The former effect of exogenous podoplanin was impaired by treatment with either JNK inhibitor sp600125 or podoplanin-siRNA, and the latter effect was impaired by treatment with podoplanin-siRNA, suggesting that podoplanin was able to activate JNK, thereby downregulating VEGF-C gene expression in LSCCs (podoplanin-JNK-VEGF-C axis). Furthermore, supporting evidence in regard to the axis present in LSCCs was obtained from similar experiments using H157 cells, another lung SCC cell line expressing endogenous podoplanin.ConclusionsOur findings suggested that LSCC-associated podoplanin was functional and could attenuate the potential for lymph node metastasis, possibly based on the suppression of tumor lymphangiogenesis; thus, podoplanin in cancer cells may become a useful biomarker to measure the malignancy of lung SCC.

【 授权许可】

Unknown   
© Suzuki et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.