Matriptase-2 inhibits breast tumor growth and invasion and correlates with favorable prognosis for breast cancer patients

Parr, Christian, Sanders, Andrew ORCID: https://orcid.org/0000-0002-7997-5286, Davies, Gaynor, Martin, Tracey ORCID: https://orcid.org/0000-0003-2690-4908, Lane, Jane ORCID: https://orcid.org/0000-0002-1926-4909, Mason, Malcolm ORCID: https://orcid.org/0000-0003-1505-2869, Mansel, Robert ORCID: https://orcid.org/0000-0002-8051-0726 and Jiang, Wen ORCID: https://orcid.org/0000-0002-3283-1111 2007. Matriptase-2 inhibits breast tumor growth and invasion and correlates with favorable prognosis for breast cancer patients. Clinical Cancer Research 13 (12) , pp. 3568-3576. 10.1158/1078-0432.CCR-06-2357

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Abstract

Purpose: The type II transmembrane serine proteases are cell surface proteolytic enzymes that mediate a diverse range of cellular functions, including tumor invasion and metastasis. Matriptase (matriptase-1) and matriptase-2 belong to the type II transmembrane serine protease family. Matriptase-1 is known to play a role in breast cancer progression, and elevated levels of matriptase-1 correlate with poor patient outcome. The role of matriptase-2 and its cellular function in cancer is unknown. This study aimed to provide new insights into the significance of matriptase-2 in cancer. Experimental Design: Matriptase-2 expression levels were assessed in a cohort of human breast cancer specimens (normal, n = 34; cancer, n = 95), in association with patient clinical variables, using both quantitative and qualitative analysis of the matriptase-2 transcript along with immunohistochemical techniques. Matriptase-2 was also experimentally overexpressed in the MDA-MB-231 human breast cancer cell line. The effects of matriptase-2 overexpression were examined through a series of in vitro and in vivo studies. Results: Here, we show that reduced matriptase-2 levels in breast cancer tissues correlate with an overall poor prognosis for the breast cancer patient. This study also reveals that matriptase-2 overexpression in breast cancer cells significantly suppressed tumorigenesis in CD1 athymic mice (P = 0.000003). Furthermore, we report that matriptase-2 overexpression dramatically reduced the invasive (P = 0.0001) and migratory properties (P = 0.01) of the breast cancer cells. Conclusions: Matriptase-2 suppresses breast tumor development in vivo, displays prognostic value for breast cancer patients, inhibits both breast cancer cell invasion and motility in vitro, and may play a contrasting role to matriptase-1 in breast cancer.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	American Association for Cancer Research
ISSN:	1078-0432
Date of Acceptance:	29 March 2009
Last Modified:	07 Feb 2023 02:23
URI:	https://orca.cardiff.ac.uk/id/eprint/77595

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