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


METHODS
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.
Parr
Christian
C
Metastasis and Angiogenesis Research Group, School of Medicine, Cardiff University, Cardiff, United Kingdom. parrc@cf.ac.uk
Sanders
Andrew J
AJ
Davies
Gaynor
G
Martin
Tracey
T
Lane
Jane
J
Mason
Malcolm D
MD
Mansel
Robert E
RE
Jiang
Wen G
WG
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism*
D008565:Membrane Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; C467801:matriptase 2