Tumor lymphangiogenesis and metastasis to lymph nodes induced by cancer cell expression of podoplanin

Cueni, Leah N; Hegyi, Ivan; Shin, Jay W; Albinger-Hegyi, Andrea; Gruber, Silke; Kunstfeld, Rainer; Moch, Holger; Detmar, Michael (2010). Tumor lymphangiogenesis and metastasis to lymph nodes induced by cancer cell expression of podoplanin. American journal of pathology, 177(2), pp. 1004-16. New York, N.Y.: Elsevier 10.2353/ajpath.2010.090703

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The membrane glycoprotein podoplanin is expressed by several types of human cancers and might be associated with their malignant progression. Its exact biological function and molecular targets are unclear, however. Here, we assessed the relevance of tumor cell expression of podoplanin in cancer metastasis to lymph nodes, using a human MCF7 breast carcinoma xenograft model. We found that podoplanin expression promoted tumor cell motility in vitro and, unexpectedly, increased tumor lymphangiogenesis and metastasis to regional lymph nodes in vivo, without promoting primary tumor growth. Importantly, high cancer cell expression levels of podoplanin correlated with lymph node metastasis and reduced survival times in a large cohort of 252 oral squamous cell carcinoma patients. Based on comparative transcriptional profiling of tumor xenografts, we identified endothelin-1, villin-1, and tenascin-C as potential mediators of podoplanin-induced tumor lymphangiogenesis and metastasis. These unexpected findings identify a novel mechanism of tumor lymphangiogenesis and metastasis induced by cancer cell expression of podoplanin, suggesting that reagents designed to interfere with podoplanin function might be developed as therapeutics for patients with advanced cancer.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Hegyi, Ivan

ISSN:

0002-9440

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:12

Last Modified:

17 Mar 2015 19:13

Publisher DOI:

10.2353/ajpath.2010.090703

PubMed ID:

20616339

Web of Science ID:

000280894600049

URI:

https://boris.unibe.ch/id/eprint/2265 (FactScience: 204656)

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