Universität zu Köln

Schwab, Melanie ORCID: 0000-0002-0208-0759, Lohr, Sabrina, Schneider, Jakob, Kaiser, Michaela, Krunic, Damir, Helbig, Doris, Geraud, Cyrill and Angel, Peter (2021). Podoplanin is required for tumor cell invasion in cutaneous squamous cell carcinoma. Exp. Dermatol., 30 (11). S. 1619 - 1631. HOBOKEN: WILEY. ISSN 1600-0625

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Abstract

The invasiveness of late-stage cutaneous squamous cell carcinoma (cSCC) is associated with poor patients' prognosis and linked to strong upregulation of the glycoprotein Podoplanin (PDPN) in cancer cells. However, the function of PDPN in these processes in cSCC carcinogenesis has not been characterized in detail yet. Employing a CRISPR/Cas9-based loss-of-function approach on murine cSCC cells, we show that the loss of Pdpn results in decreased migration and invasion in vitro. Complementing these in vitro studies, labelled murine control and Pdpn knockout cells were injected orthotopically into the dermis of nude mice to recapitulate the formation of human cSCC displaying a well-differentiated morphology with a PDPN-positive reaction in fibroblasts in the tumor stroma. Smaller tumors were observed upon Pdpn loss, which is associated with reduced tumor cell infiltration into the stroma. Utilizing Pdpn mutants in functional experiments in vitro, we provide evidence that both the intra- and extracellular domains are essential for cancer cell invasion. These findings underline the critical role of PDPN in cSCC progression and highlight potential therapeutic strategies targeting PDPN-dependent cancer cell invasion, especially in late-stage cSCC patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schwab, Melanie UNSPECIFIED orcid.org/0000-0002-0208-0759 UNSPECIFIED Lohr, Sabrina UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Jakob UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Krunic, Damir UNSPECIFIED UNSPECIFIED UNSPECIFIED Helbig, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED Geraud, Cyrill UNSPECIFIED UNSPECIFIED UNSPECIFIED Angel, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-584663
DOI:	10.1111/exd.14344
Journal or Publication Title:	Exp. Dermatol.
Volume:	30
Number:	11
Page Range:	S. 1619 - 1631
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1600-0625
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58466