Up-Regulation of the Lymphatic Marker Podoplanin, a Mucin-Type Transmembrane Glycoprotein, in Human Squamous Cell Carcinomas and Germ Cell Tumors

Abstract

The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but not blood vascular endothelial cells in culture and in tumor-associated lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning. However, research into the biological importance of podoplanin has been hampered by the lack of a generally available antibody against the human protein, and its expression in normal tissues and in human malignancies has remained unclear. We generated a human podoplanin-Fc fusion protein and found that the commercially available mouse monoclonal antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme-linked immunosorbent assay and Western blot analyses. We found that, in addition to lymphatic endothelium, podoplanin was also expressed by peritoneal mesothelial cells, osteocytes, glandular myoepithelial cells, ependymal cells, and by stromal reticular cells and follicular dendritic cells of lymphoid organs. These findings were confirmed in normal mouse tissues with anti-podoplanin antibody 8.1.1. Podoplanin was also strongly expressed by granulosa cells in normal ovarian follicles, and by ovarian dysgerminomas and granulosa cell tumors. Although podoplanin was primarily absent from normal human epidermis, its expression was strongly induced in 22 of 28 squamous cell carcinomas studied. These findings suggest a potential role of podoplanin in tumor progression, and they also identify the first commercially available antibody for the specific staining of a defined lymphatic marker in archival human tissue sections, thereby enabling more widespread studies of tumor lymphangiogenesis in human cancers.

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

“…[15][16][17][18][19][20][21] These findings suggest that podoplanin plays a role in the progression of epithelial cancer. However, the exact molecular function of cancer cell-expressed podoplanin is currently studied.…”

Differential gene expression profiles of neurothekeomas and nerve sheath myxomas by microarray analysis

“…These genes are involved in extracellular matrix growth and remodeling, and cell adhesion in fibroblasts and macrophages (Table 6). [49][50][51][52][53][54][55][56] There were relatively few statistically significant genes differentially expressed between neurothekeomas and cellular fibrous histiocyomas, and between nerve sheath myxomas and schwannomas. For neurothekeomas and cellular fibrous histiocytomas, these genes primarily included various collagen proteins.…”

Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis

“…Recently, however, Schacht et al (2005) found that D2-40 and podoplanin detect the same protein on LECs. As both markers showed the same intensity of staining, and the same pattern, either can be used to generate the same results.…”