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PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma

Keratinocyte-Expressed Podoplanin is Dispensable for Multi-Step Skin Carcinogenesis

Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Vladimir-Prelog-Weg 3, HCI H303, 8093 Zürich, Switzerland
Department of Pathology and Molecular Pathology, University and University Hospital Zurich, 8091 Zurich, Switzerland
School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do, Korea
Author to whom correspondence should be addressed.
Cells 2020, 9(6), 1542;
Received: 10 April 2020 / Revised: 21 June 2020 / Accepted: 21 June 2020 / Published: 24 June 2020
(This article belongs to the Special Issue Structure and Function of Podoplanin (PDPN) in Disease)
Podoplanin is a small transmembrane mucin-like glycoprotein that plays a crucial role in the development of the lung, heart and lymphatic vascular system. Its expression is upregulated in several types of human carcinomas and podoplanin levels in squamous cell carcinomas (SCCs) of the oral cavity and the lung correlate with cancer invasiveness, lymph node metastasis and shorter survival time of patients, indicating that podoplanin promotes tumor progression. However, its role during the early stages of carcinogenesis remain unclear. We generated mice with a specific deletion of podoplanin in epidermal keratinocytes (K5-Cre;Pdpnflox/flox mice) and subjected them to a multistep chemical skin carcinogenesis regimen. The rate of tumor initiation; the number, size and differentiation of tumors; and the malignant transformation rate were comparable in K5-Cre;Pdpnflox/flox mice and Pdpnflox/flox control mice. However, tumor cell invasion was reduced in K5-Cre;Pdpnflox/flox mice, in particular single cell invasion. Quantitative immunofluorescence analyses revealed that peritumoral lymphangiogenesis was reduced in K5-Cre;Pdpnflox/flox mice, whereas there were no major changes of tumor-associated immune cell subpopulations. Thus, keratinocyte-expressed podoplanin is dispensable for the early steps of skin carcinogenesis but contributes to the progression of established tumors. View Full-Text
Keywords: carcinogenesis; podoplanin; lymphangiogenesis; keratinocytes carcinogenesis; podoplanin; lymphangiogenesis; keratinocytes
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MDPI and ACS Style

Sesartić, M.; Ikenberg, K.; Yoon, S.-Y.; Detmar, M. Keratinocyte-Expressed Podoplanin is Dispensable for Multi-Step Skin Carcinogenesis. Cells 2020, 9, 1542.

AMA Style

Sesartić M, Ikenberg K, Yoon S-Y, Detmar M. Keratinocyte-Expressed Podoplanin is Dispensable for Multi-Step Skin Carcinogenesis. Cells. 2020; 9(6):1542.

Chicago/Turabian Style

Sesartić, Marko, Kristian Ikenberg, Sun-Young Yoon, and Michael Detmar. 2020. "Keratinocyte-Expressed Podoplanin is Dispensable for Multi-Step Skin Carcinogenesis" Cells 9, no. 6: 1542.

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